STANDAR NASIONAL AKREDITASI RUMAH SAKIT EDISI 1

Pengelompokan Standar Nasional Akreditasi Rumah Sakit Edisi 1

Standar dikelompokkan menurut fungsi-fungsi penting yang umum dalam organisasi
perumahsakitan. Pengelompokan berdasarkan fungsi, saat ini paling banyak
digunakan di seluruh dunia.
Standar dikelompokkan menurut fungsi-fungsi yang terkait dengan penyediaan
pelayanan bagi pasien; juga dengan upaya menciptakan organisasi rumah sakit yang
aman, efektif, dan terkelola dengan baik. Fungsi-fungsi tersebut tidak hanya berlaku
untuk rumah sakit secara keseluruhan tetapi juga untuk setiap unit, departemen, atau
layanan yang ada dalam organisasi rumah sakit tersebut. Lewat proses survei
dikumpulkan informasi sejauh mana seluruh organisasi mentaati pedoman yang
ditentukan oleh standar. Keputusan pemberian akreditasinya didasarkan pada tingkat
kepatuhan terhadap standar di seluruh organisasi rumah sakit yang bersangkutan.
Pengelompokan Standar Nasional Akreditasi Rumah Sakit Edisi 1 (SNARS Edisi 1)
sebagai berikut:

SASARAN KESELAMATAN PASIEN
SASARAN 1 : Mengidentifikasi pasien dengan benar
SASARAN 2 : Meningkatkan komunikasi yang efektif
SASARAN 3 : Meningkatkan keamanan obat-obatan yang harus
diwaspadai (High Alert Medications)
SASARAN 4 : Memastikan lokasi pembedahan yang benar,
prosedur yang benar, pembedahan pada
pasien yang benar.
SASARAN 5 : Mengurangi risiko infeksi terkait
pelayanan kesehatan
SASARAN 6 : Mengurangi risiko cedera pasien akibat terjatuh

II. STANDAR PELAYANAN BERFOKUS PASIEN
Akses ke Rumah Sakit dan Kontinuitas Pelayanan (ARK)
Hak Pasien dan Keluarga (HPK)
Asesmen Pasien (AP)
Pelayanan dan Asuhan Pasien (PAP)
Pelayanan Anestesi dan Bedah (PAB)
Pelayanan Kefarmasian dan Penggunaan Obat (PKPO)
Manajemen Komunikasi dan Edukasi (MKE)

III. STANDAR MANAJEMEN RUMAH SAKIT

Peningkatan Mutu dan Keselamatan Pasien (PMKP)
Pencegahan dan Pengendalian Infeksi (PPI)
Tata Kelola Rumah Sakit (TKRS)
Manajemen Fasilitas dan Keselamatan (MFK)
Kompetensi dan Kewenangan Staf (KKS)
Manajemen Informasi dan Rekam Medis (MIRM)

IV. PROGRAM NASIONAL
Menurunkan Angka Kematian Ibu dan Bayi.
Menurukan Angka Kesakitan HIV/AIDS.
Menurukan Angka Kesakitan TB
Pengendalian Resistensi Antimikroba (PPRA)
Pelayanan Geriatri

JCI 6th standards for hospitals

Joint Commission International
A division of Joint Commission Resources, Inc.
The mission of Joint Commission International (JCI) is to improve the safety and quality of care in the
international community through the provision of education, publications, consultation, and evaluation
services. Joint Commission Resources educational programs and publications support, but are separate from,
the accreditation activities of Joint Commission International. Attendees at Joint Commission Resources
educational programs and purchasers of Joint Commission Resources publications receive no special
consideration or treatment in, or confidential information about, the accreditation process.
© 2017 Joint Commission International
All rights reserved. No part of this publication may be reproduced in any form or by any means without
written permission from the publisher.
Printed in the U.S.A. 5 4 3 2 1
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permissions@jcrinc.com
ISBN: 978-1-59940-989-4
Library of Congress Control Number: 2013948698
For more information about Joint Commission Resources, please visit http://www.jcrinc.com.
For more information about Joint Commission International, please visit
http://www.jointcommissioninternational.org

Contents
Standards Advisory Panel................................................................................................. v
Introduction....................................................................................................................1
General Eligibility Requirements.....................................................................................7
Summary of Changes to the Manual ...............................................................................9
Section I: Accreditation Participation Requirements ...............................................31
Accreditation Participation Requirements (APR)................................................33
Section II: Patient-Centered Standards....................................................................41
International Patient Safety Goals (IPSG) ..........................................................43
Access to Care and Continuity of Care (ACC) ...................................................57
Patient and Family Rights (PFR)........................................................................77
Assessment of Patients (AOP).............................................................................91
Care of Patients (COP) ....................................................................................119
Anesthesia and Surgical Care (ASC).................................................................141
Medication Management and Use (MMU)......................................................155
Patient and Family Education (PFE) ................................................................173
Section III: Health Care Organization Management Standards.............................177
Quality Improvement and Patient Safety (QPS)...............................................179
Prevention and Control of Infections (PCI) .....................................................191
Governance, Leadership, and Direction (GLD)................................................207
Facility Management and Safety (FMS)............................................................237
Staff Qualifications and Education (SQE)........................................................257
Management of Information (MOI) ................................................................285
Section IV: Academic Medical Center Hospital Standards.....................................301
Medical Professional Education (MPE)............................................................303
Human Subjects Research Programs (HRP) .....................................................309
Summary of Key Accreditation Policies .......................................................................317
Glossary ......................................................................................................................327
Index...........................................................................................................................339

Standards Advisory
Panel
John Øvretveit, BSc(hons), MPhil, PhD,
CPsychol, CSci, MHSM (Chairperson)
Stockholm, Sweden

Abdullah Mufareh Assiri, MD
Riyadh, Saudi Arabia

María del Mar Fernández, MSc, PhD
Madrid, Spain

Brigit Devolder, MS
Leuven, Belgium

Samer Ellahham, MD, FACP, FACC, FAHA,
FCCP, ASHCSH
Abu Dhabi, UAE

Paul Hofmann, DrPH, FACHE
California, USA

Johan Kips, MD, PhD
Brussels, Belgium

Manish Kohli, MD, MPH, MBA
Abu Dhabi, UAE

Lee Chien Earn, PhD
Singapore

Harish Pillai, MD
Kerala, India

Abdul Latif Sheikh, MS, RPh
Karachi, Pakistan

Abha Shroff, MBBS, MD, DCP
Mumbai, India

José Valverde Filho, MD
Rio De Janeiro, Brazil

Introduction
Joint Commission International (JCI) is proud to publish the 6th edition of the Joint Commission International
Accreditation Standards for Hospitals. Each of the five previous editions have sought to reflect the most current
thinking in patient safety practices and concepts to help accredited and nonaccredited organizations uncover
their most pressing safety risks and advance their goals for continuous quality improvement. This tradition
carries on with the 6th edition as it seeks to continue the work of making health care as safe as possible.
The Joint Commission International Accreditation Standards for Hospitals contain the standards, intents,
measurable elements (MEs), a summary of changes for this edition of the JCI hospital standards, a summary
of key accreditation policies and procedures, a glossary of terms, and an index. This introduction is designed to
provide information on the following topics:
• The origin of these standards
• How the standards are organized
• How to use this standards manual
• What is new in this edition of the manual

If, after reading this publication, you have questions about the standards or the accreditation process, please
contact JCI:
+1-630-268-7400
JCIAccreditation@jcrinc.com
How were the standards developed and refined
for this 6th edition?
The JCI standards development process is a collaboration between JCI, accredited organizations, and experts
in quality and safety. This new edition takes into account developments in the science of quality improvement
and patient safety as well as the experiences of the organizations that used the 5th edition hospital standards to
improve the safety and quality of care in their organizations.
The development process included the following:
• Focus groups with JCI–accredited organization leaders and other health care experts. These focus
groups were conducted in 16 countries, in regions around the world.
• Review of the literature for current evidence-based practice and processes, and authoritative sources
for industry guidelines, to support new and revised standards
• Input from experts and others with specific and relevant content knowledge, including JCI surveyors
and consultants
• Discussion and guidance on the development and revision of the standards with the Standards
Advisory Panel, a 13-member international panel composed of experts with extensive experience in
various health care fields
• An online field review of the draft 6th edition standards sent to all accredited hospitals and JCI field
staff and promoted through social media and the JCI website.

How are the standards organized?
The standards are organized around the important functions common to all health care organizations. This
approach is now the most widely used around the world and has been validated by scientific study, testing, and
application.
The standards are grouped into three major areas: those related to providing patient care; those related to
providing a safe, effective, and well-managed organization; and, for academic medical center hospitals only,
those related to medical professional education and human subjects research programs. The standards apply
to the entire organization as well as to each department, unit, or service within the organization. The survey
process gathers standards compliance information throughout the entire organization, and the accreditation
decision is based on the organization’s overall level of compliance.

What are the Academic Medical Center hospital
standards and do they apply to my organization?
The Academic Medical Center (AMC) hospital standards were developed and first published in 2012
to recognize the unique resource such centers represent for health professional education and human
subjects research in their community and country. This section of standards contains two chapters: Medical
Professional Education (MPE) and Human Subjects Research Programs (HRP). Unless deliberately included
in the quality framework, education and research activities often are the unnoticed partners in patient care
quality monitoring and improvement. To address this concern, the standards in these two chapters present
a framework for including medical education and research into the quality and patient safety activities of
academic medical center hospitals.
Many health care organizations may consider themselves to be academic medical centers. However, only
organizations that meet JCI’s definition are required to comply with the standards present in the AMC section
of the manual. Academic medical center hospital applicants must meet each of the following three criteria:
1. The applicant hospital is organizationally or administratively integrated with a medical school.
2. The applicant hospital is the principal site for the education of both medical students (undergraduates)
and postgraduate medical specialty trainees (for example, residents or interns) from the medical
school noted in criterion 1.
3. At the time of application, the applicant hospital is conducting medical research with approval and
oversight by an Institutional Review Board (IRB) or research ethics committee.
All hospitals meeting the eligibility criteria must comply with the requirements in these two chapters (as well as
the other requirements detailed in this manual) in order to be accredited by JCI.
Organizations with questions about their eligibility for Academic Medical Center hospital accreditation should
contact JCI Accreditation’s Central Office at jciaccreditation@jcrinc.com.

Are the standards available for the international
community to use?
Yes. These standards are available in the international public domain for use by individual health care
organizations and by public agencies seeking to improve the quality of patient care. To assist such
organizations, JCI has provided a document that lists the standards (but not the intent statements and MEs)
that can be downloaded at no cost from the JCI website. The translation and use of the standards as published
by JCI requires written permission.

When there are national or local laws related to a
standard, what applies?
When a concept is addressed by the JCI standards and by the laws or regulations of a national or local
authority, JCI requires that an organization follow whichever body has set the higher or stricter requirement.
For example, JCI requires that organizations use two patient identifiers in a variety of processes. If the
hospital’s national standard requires the use of three identifiers, the hospital must consequently use three
identifiers to meet the national standard which is stricter than JCI’s standard. However, if that same national
standard allows the use of bed number as an identifier—a practice JCI explicitly prohibits—the organization is
prohibited from doing so. In this case, the organization would need to use three identifiers (the stricter national
requirement) and would be prohibited from using bed number as an identifier (the stricter JCI requirement).

How do I use this standards manual?
This international standards manual can be used to accomplish the following:
• Guide the efficient and effective management of a health care organization
• Guide the organization and delivery of patient care services and efforts to improve the quality and
efficiency of those services
• Review the important functions of a health care organization
• Become aware of those standards that all organizations must meet to be accredited by JCI
• Review the compliance expectations of the standards as well as those of the additional requirements
found in the associated intent
• Become aware of the accreditation policies and procedures and the accreditation process
• Become familiar with the terminology used in the manual
JCI requirements by category are described in detail below. JCI’s policies and procedures are also summarized
in this manual. Please note that these are neither the complete list of policies nor every detail of each policy.
Current JCI policies are published on JCI’s public website, www.jointcommissioninternational.org.
JCI Requirement Categories
JCI requirements are described in these categories:
• Accreditation Participation Requirements (APR)
• Standards
• Intents
• Measurable Elements (MEs)

Accreditation Participation Requirements (APR)
The Accreditation Participation Requirements (APR) chapter is composed of specific requirements for
participation in the accreditation process and for maintaining an accreditation award. Hospitals must be
compliant with the APRs at all times during the accreditation process. However, APRs are not scored like
standards during the on-site survey; hospitals are considered either compliant or not compliant with the APRs.
When a hospital is not compliant with a specific APR, the hospital will be required to become compliant or
risk losing accreditation.

Standards
JCI standards define the performance expectations, structures, or functions that must be in place for a hospital
to be accredited by JCI. JCI’s standards are evaluated during the on-site survey.

Intents
A standard’s intent helps explain the full meaning of the standard. The intent describes the purpose and
rationale of the standard, provides an explanation of how the standard fits into the overall program, sets parameters for the requirement(s), and otherwise “paints a picture” of the requirements and goals. The bulleted
lists in the intent statement are considered advisory and serve as a helpful explanation of practices that might
meet the standard. Numbered or lettered lists in the intent statement include required elements that must be in
place in order to meet the standard.

Measurable Elements (MEs)
Measurable elements (MEs) of a standard indicate what is reviewed and assigned a score during the on-site
survey process. The MEs for each standard identify the requirements for full compliance with the standard.
The MEs are intended to bring clarity to the standards and help the organization fully understand the
requirements, educate leadership, department/service leaders, health care practitioners, and staff about the
standards, and guide the organization in accreditation preparation.
Other Sections Included in This Manual
• General Eligibility Requirements
• Summary of Changes to the Manual
• Summary of Key Accreditation Policies
• Glossary
• Index

What is new in this 6th edition of the manual?
There are many changes to this 6th edition of the hospital manual. A thorough review is strongly recommended.
This 6th edition of the hospital manual includes a summary of changes to the manual immediately preceding
the Accreditation Participation Requirements chapter. This summary identifies new standards, new measurable
elements, an explanation of the changes, as well as text that has been edited from the 5th edition for the
purpose of providing increased clarity and additional examples. Other changes to the hospital manual include:
• Updated and additional evidence-based references to support the new and revised standards. With
this feature, JCI is continuing to provide support for its standards by citing important evidence that
provides assistance with compliance. References of various types—from clinical research to practical
guidelines—are cited in the text of the standard’s intent and are listed at the end of the applicable
standard chapter.
• Modifications to the APR chapter.
• A P icon added after the standard text in some standards, such as some new standards in the 6th
edition. As in the 5th edition, some standards require the hospital to have a policy, procedure, or other
type of written document for specific processes. Those standards are indicated by a P icon after the
standard text. All written policies, procedures, and programs will be scored together at MOI.8 and
MOI.8.1.
• More examples added to many standards’ intents to better illustrate expectations for compliance. To
make the examples more apparent to the user, the term for example is printed in bold text.
• Definitions of key terms used throughout the manual have been created or updated, and text
including those terms has been reevaluated and revised to ensure that terminology is correct and clear.
Many terms are defined within intents; look for these key terms in italics (for example, leadership).
All key terms are defined in the glossary in the back of this edition.
• Chapter overviews and lists of “standards only” have returned to this edition and are presented at the
beginning of each chapter.

How frequently are the standards updated?
Information and experience related to the standards will be gathered on an ongoing basis. If a standard no
longer reflects contemporary health care practice, commonly available technology, quality management
practices, and so forth, it will be revised or deleted. It is current practice that the standards are revised and
published approximately every three years.

What does the “effective” date on the cover of this
6th edition of the standards manual mean?
The “effective” date found on the cover means one of two things:
1. For hospitals accredited under the 5th edition of the standards, this is the date by which they now
must be in full compliance with all the standards in the 6th edition. Standards are published at least six
months in advance of the effective date to provide time for organizations to come into full compliance
with the revised standards by the time they are effective.
2. For hospitals seeking accreditation for the first time, the effective date indicates the date after which
all surveys and accreditation decisions will be based on the standards of the 6th edition. Any survey and
accreditation decisions before the effective date will be based on the standards of the 5th edition.

General Eligibility Requirements
Any hospital may apply for Joint Commission International (JCI) accreditation if it meets all the following
criteria:
• The hospital is located outside of the United States and its territories.
• The hospital is currently operating as a health care provider in the country, is licensed to provide care
and treatment as a hospital (if required), and, at minimum, does the following:
>Provides a complete range of acute care clinical services—diagnostic, curative, and rehabilitative.
>In the case of a specialty hospital, provides a defined set of services, such as pediatric, eye, dental,
and psychiatry, among others.
>For all types of hospitals, provides services that are available 365 days per year; ensures all direct
patient care services are operational 24 hours per day, 7 days per week; and provides ancillary
and support services as needed for emergent, urgent, and/or emergency needs of patients 24
hours per day, 7 days per week (such as diagnostic testing, laboratory, and operating theatre, as
appropriate to the type of acute care hospital).
• The hospital provides services addressed by the current JCI accreditation standards for hospitals.
• The hospital assumes, or is willing to assume, responsibility for improving the quality of its care and
services.
• The hospital is open and in full operation, admitting and discharging a volume of patients that will
permit the complete evaluation of the implementation and sustained compliance with all current JCI
accreditation standards for hospitals.
• The hospital meets the conditions described in the current Accreditation Participation Requirements
(APRs).
Academic medical center hospital applicants must meet each of the criteria above in addition to the following
three criteria:
1) The applicant hospital is organizationally or administratively integrated with a medical school.
2) The applicant hospital is the principal site for the education of both medical students (undergraduates)
and postgraduate medical specialty trainees (for example, residents or interns) from the medical
school noted in criterion 1.
3) At the time of application, the applicant hospital is conducting medical research with approval and
oversight by an Institutional Review Board (IRB) or research ethics committee.
Definitions
Full operation
• The hospital accurately identifies the following in its electronic application (E-App) at the time of
application:
> All clinical services currently provided for inpatients and outpatients. (Those clinical services that
are planned and thus not identified in the E-App and begin operations at a later time will require
a separate extension survey to evaluate those services.)
> Utilization statistics for clinical services showing consistent inpatient and outpatient activity
levels and types of services provided for at least four months or more prior to submission of the
E-App
• All inpatient and outpatient clinical services, units, and departments identified in the E-App are
available for a comprehensive evaluation against all relevant JCI standards for hospitals currently
in effect, consistent with JCI’s normal survey process for the size and type of organization (see, for
example, the current JCI hospital survey process guide), such as
>patient tracer activities, including individual patient and system tracers;
>open and closed medical record review;
>direct observation of patient care processes;
>interviews with patients; and
>interviews with medical students/trainees.

Contact JCI Accreditation prior to submitting an E-App to discuss the criteria and validate whether the
hospital meets the above criteria for “in full operation” at least four months or more prior to submitting its
E-App and at its initial survey. JCI may request documentation of the hospital’s utilization statistics prior to
accepting the E-App or conducting the on-site survey. In addition, JCI will not begin an on-site survey, may
discontinue an on-site survey, or may cancel a scheduled survey when it determines the hospital is not “in full
operation.”

Principal site
Principal site means the hospital provides the majority of medical specialty programs for postgraduate medical
trainees (for example, residents or interns) and not just one specialty, as in a single-specialty hospital (for
example, an ophthalmologic hospital, dental hospital, or orthopedic hospital).

Medical research
Medical research conducted at the academic medical center hospital represents varied medical areas or
specialties within the institution and includes basic, clinical, and health services research. Such research may
include clinical trials, therapeutic interventions, development of new medical technologies, and outcomes
research, among others. Hospitals that primarily conduct non–human subjects research and/or research exempt
from review by an IRB or research ethics committee, such as medical record review studies, case studies, and
research involving data/specimens without individually identifiable information, do not meet criterion 3 of the academic medical center hospital eligibility criteria.

Note: If in its reasonable discretion JCI determines that the applicant does not meet the eligibility criteria for
the Hospital/Academic Medical Center Hospital accreditation program, JCI will not accept the application or
will not process the application for accreditation from the hospital and will notify the hospital of its decision.

Snake bite managemen

Gigitan ular di Afrika bagian selatan: diagnosis dan manajemen

Ada tiga kelompok ular berbisa di Afrika bagian selatan - sitotoksik, neurotoksik dan hemotoksik.

GJ Müller, BSc, MB ChB, Hons BSc (Pharm), MMed (Anaes), PhD (Tox)

Dr Müller adalah konsultan paruh waktu di Divisi Farmakologi, Departemen Kedokteran, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Stellenbosch. Dia adalah pendiri Pusat Informasi Racun Tygerberg.

H Modler, Dip Pharm (Farmasi), BSc, MB ChB, MMed (Anaes)

Dr Modler adalah seorang ahli anestesi dalam praktik pribadi, juga sebagai dosen paruh waktu dan pemeriksa eksternal dalam bidang farmakologi di Departemen Anestesi, Universitas Stellenbosch dan Kolese Kedokteran Afrika Selatan.

CA Wium, MSc Ilmu Kesehatan

Ms Wium adalah seorang ilmuwan medis utama yang dipekerjakan sebagai ahli toksikologi di Pusat Informasi Racun Tygerberg, Divisi Farmakologi, Departemen Kedokteran, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Stellenbosch.

DJH Veale, PhD Farmakologi

Dr Veale adalah mantan direktur Pusat Informasi Racun Tygerberg dan saat ini menjadi konsultan apoteker klinis dan dosen farmakologi dan toksikologi.

CJ Marks, BSc Pharmacy, MSc Ilmu Kesehatan

Ms Marks adalah direktur Pusat Informasi Poison Tygerberg, Divisi Farmakologi, Departemen Kedokteran, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Stellenbosch.

Korespondensi ke: Gert Müller (gmul@sun.ac.za)

Ular berbisa di Afrika bagian selatan dapat dibagi dalam 3 kelompok: sitotoksik, neurotoksik dan yang dapat menyebabkan efek toksik haemostatik. Namun, tumpang tindih efek ini bisa terjadi. Beberapa spesies ular dapat, misalnya, menampilkan baik sitotoksisitas dan neurotoksisitas.

Lihat Tabel 1 di akhir artikel untuk klasifikasi, distribusi, habitat dan toksinologi klinis ular berbisa di Afrika bagian selatan.

Identifikasi ular yang bertanggung jawab atas gigitan biasanya sulit dilakukan, kecuali seekor ular mati dibawa ke rumah sakit dengan korbannya dan dapat diidentifikasi dengan andal. Deskripsi ular dan keadaan gigitan mungkin menyarankan diagnosis spesies, namun ini tidak sering merupakan dasar yang memuaskan untuk pengobatan spesifik.

Dalam kebanyakan kasus gigitan ular, manajemen klinis yang sesuai memerlukan identifikasi sindrom klinis khusus berdasarkan data epidemiologis, klinis dan laboratorium. Oleh karena itu, pendekatan sindromik direkomendasikan pada sebagian besar kasus.

Sindrom klinis utama

Lima sindroma klinis utama envenoming ular diakui di Afrika bagian selatan:

• Nyeri lokal ditandai dan pembengkakan progresif yang terkait dengan perubahan kulit sitotoksik yang menonjol dengan darah yang dapat dikoagulasi

• Kelumpuhan progresif (neurotoksisitas), dengan pembengkakan lokal yang tidak berarti atau kecil

• darah yang tidak bisa diobati, dengan mudah terbengkalai pada bengkak lokal ringan

• pembengkakan lokal sedang sampai ditandai, berhubungan dengan neurotoksisitas

• pembengkakan ringan sampai sedang, dengan gejala sistemik yang tidak berarti atau tidak ada.

Nyeri lokal ditandai dan pembengkakan progresif yang terkait dengan perubahan kulit sitotoksik yang menonjol dengan darah yang dapat dikoagulasi

Ular yang bertanggung jawab atas sindrom ini meliputi:

• Penambah utama, misalnya Bitis arietans (puff adder) dan B. gabonica (gabon adder) (Gambar 1 dan 2).

• Meludah kobra, misalnya Naja mossambica (lobak meludah kobra, M'fesi), N. nigricollis (kobra melonjak berleher hitam), N. nigricincta (batromus melonjak, zebra spitting cobra) dan N. nigricincta woodi (kobra meludah hitam) (Gambar 3 - 5).

• Rinkhals, Hemachatus haemachatus. Meskipun efek neurotoxic ringan telah disebutkan terjadi pada gigitan rinkhals, ini belum didokumentasikan dengan baik (Gambar 6).

(Perlu dicatat bahwa sitotoksisitas ekstensif dengan neurotoksisitas yang tidak signifikan telah dijelaskan setelah gigitan mamba hijau Afrika Selatan.)

Untuk informasi lebih lanjut mengenai klasifikasi, morfologi, habitat dan distribusi ular yang disebut di atas, lihat Tabel 1 dan Gambar 7 dan 8.

Racun racun ular sitotoksik adalah hidrolase pencernaan (enzim proteolitik dan fosfolipase) dan polipeptida yang menghancurkan selaput sel, otot rangka dan jaringan lainnya. Efek ini meningkatkan permeabilitas endotelium vaskular, yang menyebabkan pembengkakan lokal, terik dan edema. Kematian jaringan yang tidak dapat diperbaiki dapat terjadi (nekrosis / gangren).

Gambaran klinis

Efek lokal dari gigitan dengan meludah kobra pada dasarnya sama dengan gigitan penambah besar. Bengkak biasanya dimulai lebih awal, seringkali dalam waktu 10 - 30 menit. Ini mungkin menjadi luas, melibatkan seluruh anggota badan dan bahkan area yang berdekatan dengan batang, terutama pada anak-anak. Kelenjar getah bening regional bisa membesar dan nyeri dalam 30 - 60 menit. Sifat sitotoksik agresif dan progresif dari envenoming biasanya terlihat beberapa jam setelah gigitannya. Lepuh dan lesi kulit bulosa, cairan atau darah terisi, dan ekimosis sering berkembang, mula-mula di dekat bekas torehan, tapi mungkin kemudian meluas melampaui lokasi gigitan dalam waktu 6 - 24 jam.

'Lewati lesi' (daerah nekrosis yang dipisahkan oleh potongan kulit yang tampaknya normal yang disebabkan oleh penyebaran racun proksimal dalam pembuluh getah bening) adalah karakteristik dari meludahnya gigitan kobra (Gambar 10). Meludah kobra sering memasuki tempat tinggal di malam hari dan sering menggigit korban saat tertidur.

Ekstravasasi plasma dapat menyebabkan hipovolemia, yang dapat menyebabkan syok hipovolemik, terutama pada anak-anak. Efek sitotoksik lokal dapat berkembang menjadi nekrosis, dengan pengelupasan spontan jaringan mati. Sindrom kompartemen dapat berkembang, terutama yang melibatkan kompartemen tibialis anterior setelah gigitan kaki dan pergelangan kaki, atau lengan bawah, di gigitan tangan atau pergelangan tangan. Komplikasi ini dapat menyebabkan nekrosis iskemik otot kompartemen dan kerusakan saraf. Akhir (2 - 3 hari pasca gigitan) gangguan hemostatik, terutama trombositopenia, telah dijelaskan pada bahan tambahan puff adder dan gaboon adder.

Gigitan penambah Gabo bisa disertai kelainan kardiovaskular, termasuk hipotensi, disritmia jantung dan syok. Untungnya gigitan ini jarang terjadi.

Gambar 9 (a - d) menunjukkan efek toksik lokal dari gigitan penambah puff. Gambar 10 menunjukkan efek meludah gigitan kobra.

Investigasi khusus

Biokimia darah abnormal, seperti peningkatan konsentrasi kreatin kinase serum dan enzim yang diturunkan dari otot lainnya, biasanya ditemukan pada envenoming parah karena kerusakan otot lokal. Gigitan penambah mayor mayor mungkin dipersulit oleh rhabdomyolysis, dengan melepaskan isi otot ke dalam plasma (myoglobinaemia), bermanifestasi dengan mioglobinurea, yang dapat menyebabkan fungsi ginjal yang terganggu. Trombositopenia juga merupakan komplikasi potensial. Investigasi khusus harus mencakup urinalisis, urea, kreatinin serum, elektrolit, dan hitung darah penuh (termasuk profil penggumpalan darah).

Racun ular ophthalmia adalah envenoming mata yang terjadi saat racun meludah ke mata (lihat di bawah perawatan tambahan).

Antivenom tersedia untuk gigitan ular-ular tersebut di atas (SAIMR Polyvalent Snakebite Antiserum SAVP).

Kelumpuhan progresif (neurotoksisitas), dengan pembengkakan lokal kecil atau kecil

Ular yang bertanggung jawab atas sindrom ini meliputi:

• Kobra Neurotoxic: Naja anchietae (kobra Mesir Anchieta), N. annulifera (cobra berbobot atau moncong), N. melanoleuca (kobra berbibir hitam dan putih) dan N. nivea (gambar kobra) (gambar 11 dan 12). Lihat Gambar 13 untuk distribusi kobra neurotoksik dan Tabel 1 untuk klasifikasi dan informasi lainnya.

• Mambas: Dendroaspis polylepis (mamba hitam) dan D. angustikeps (umum, hijau timur, mamba putih). Perlu dicatat bahwa sitotoksisitas yang luas dengan neurotoksisitas yang tidak signifikan telah dijelaskan setelah gigitan mamba hijau Afrika Selatan (Gambar 14 dan 15). Lihat Gambar 16 untuk distribusi mambas dan Tabel 1 untuk klasifikasi dan informasi lainnya.

Venom kobra neurotoksik mengandung polipeptida yang bersaing dengan asetilkolin untuk mengikat reseptor nikotin pasca-sinaptik pada sambungan saraf otot rangka, yang menyebabkan kelumpuhan seperti kurangka. Racun Mamba, selain pengaruhnya terhadap reseptor nikotin pasca-sinaptik, juga mengandung racun polipeptida, yang memfasilitasi pelepasan asetilkolin dari ujung saraf (dendrotoxins), serta toksin yang menghambat asetilkolinesterase sinaptik (fasciculin). Neurotoxin yang menghalangi reseptor muskarinik juga telah dijelaskan dalam racun mamba. Lihat Gambar.

Gambaran klinis

Neurotoksisitas ditandai dengan kelumpuhan lesi progresif dan menurun. Gejala dan tanda awal meliputi parestesi sementara lidah dan bibir, penglihatan kabur dan penglihatan ganda, ptosis, kelainan pupil (misalnya pupil yang melebar), ophthalmoplegia eksternal dan internal dan kelumpuhan otot wajah dan otot lainnya yang diinervasi oleh saraf kranial, yang menyebabkan disartria, dysphonia, dan disfagia. Ada peningkatan sekresi oro-pharyngeal karena sulit menelan. Hal ini diikuti oleh kelumpuhan progresif dan menurun, dan akhirnya gagal napas. Saat tekanan pernafasan meningkat, pasien menjadi cemas, berkeringat dan sianosis dan akan mati kecuali diberi ventilasi. Ular neurotoksik dapat menyebabkan kelumpuhan dan kematian yang mengancam jiwa dalam waktu 1 - 8 jam. Kegagalan pernapasan biasanya merupakan penyebab utama kematian. Gambar 17 menggambarkan ptosis setelah gigitan kobra Cape.

Selain efek neurotoksik di atas, pasien yang digigit mambas dapat hadir dengan gemetar, fasciculations otot skelet dan tanda-tanda stimulasi sistem saraf otonom (karena peningkatan aktivitas asetilkolin di celah sinaptik - lihat mekanisme di atas). Gambaran awal adalah muntah, dada dan nyeri tungkai dan air liur berlebih. Disritmia jantung juga telah dijelaskan pada korban gigitan mamba.

Pasien yang digigit oleh ular neurotoxic elapid dapat hadir dengan rasa sakit di tempat gigitan dan berbagai tingkat pembengkakan lokal kecil. Namun, pada beberapa pasien yang teracuni tempat gigitan sulit ditemukan / diidentifikasi. Nekrosis dan efek sitotoksik lokal lainnya biasanya tidak berkembang sampai tingkat signifikan. Gambar 18 menunjukkan pembengkakan lokal minimal dengan gigitan kobra Cape, sementara Gambar 19 menunjukkan bahwa pada beberapa kasus pasien kobra Cape yang diampuni, lokasi gigitan sulit ditemukan / diidentifikasi.

Investigasi khusus, jika sesuai, harus mencakup gas darah arteri dan tes fungsi pernapasan lainnya dan EKG.

Diferensial diagnosis gigitan ular neurotoxic

Diagnosis gigitan ular neurotoksik elapid, terutama bila pasien tidak sadar akan digigit atau di mana pelakunya belum diidentifikasi, terkadang sulit dilakukan. Kondisi klinis yang harus diperhatikan dalam diagnosis banding meliputi kalajengking dan latrodektisme. Lihat Tabel 1 di artikel sengatan kalajengking untuk perbandingan gejala dan tanda utama kalajengking, latrodektisme dan gigitan kobra neurotoxic. Pada penukar lemak neurotoksik / sitotoksik yang menggigit komponen sitotoksik envenoming cukup menonjol bila dibandingkan dengan efek lokal minimal dari gigitan ular neurotoksik elapid.

Antivenom tersedia untuk gigitan ular-ular tersebut di atas (SAIMR Polyvalent Snakebite Antiserum SAVP).

Darah yang tidak bisa diobati, dengan mudah terbengkalai pada bengkak lokal ringan

Ular yang bertanggung jawab atas sindrom ini meliputi:

• boomslang (Dispholidus typus) (Gambar 20 dan 21)

• Rusa selatan Savanna / ular burung / ranting (Thelotornis capensis)

• Ular savanna Oate Oate (Thelotornis capensis oatesi).

Gambar 21 menunjukkan posisi taring boomslang. Lihat Gambar 22 dan Tabel 1 untuk distribusi boomslang dan ular burung.

Venom dari boomslang memiliki efek pro-koagulan yang ampuh dengan mengaktifkan faktor II (protrombin), X dan mungkin juga IX. Koagulopati konsumtif yang parah berkembang dalam beberapa jam (4 - 24 jam) setelah gigitan. Lihat Gambar 23, di mana kaskade koagulasi darah digambarkan.

Gambaran klinis

Penderita mungkin mengalami mual, muntah, sakit perut, sakit kepala, pusing dan pingsan. Suntikan darah yang terus menerus dari fang tusukan atau tempat luka lainnya sering diamati. Meskipun pendarahan dapat terjadi dalam waktu 6 - 24 jam setelah gigitan, gejala hemostatik sistemik dan tanda dapat tertunda selama lebih dari 24 jam, bahkan beberapa hari setelah gigitan. Perdarahan biasanya bermanifestasi sebagai perdarahan gingiva, epistaksis, purpura, hematemesis, melaena, hematuria, ekimosis ekstensif, dan pada kasus yang parah, subarachnoid atau perdarahan intraserebral. Koagulopati konsumtif yang parah dapat menyebabkan kegagalan organ multipel.

Investigasi khusus mengungkapkan darah yang tidak dapat diobati, defibrinasi, peningkatan produk degradasi fibrinogen, trombositopenia dan anemia. Darah yang tidak dapat diobati merupakan tanda utama koagulopati konsumtif. Untuk memastikannya, '20 minute whole blood clotting test 'adalah tes koagulabilitas darah sederhana yang cepat, yang dapat dilakukan di samping tempat tidur dan berkorelasi dengan baik dengan konsentrasi fibrinogen. Beberapa mililiter darah yang diambil oleh venepuncture ditempatkan di dalam wadah gelas baru yang bersih dan kering dan dibiarkan tidak terganggu pada suhu kamar selama 20 menit, lalu dimiringkan sekali untuk melihat apakah darah tersebut telah tergumpal atau tidak. Tes laboratorium lain yang lebih sensitif termasuk waktu protrombin (sering dilaporkan sebagai INR), tingkat trombin dan fibrinogen, waktu tromboplastin parsial teraktivasi dan pengukuran produk degradasi fibrinogen dan konsentrasi D-dimer. Investigasi laboratorium lainnya harus mencakup urinalisis, hitung darah lengkap, urea dan elektrolit dan kreatinin serum.

Antivenom tersedia untuk gigitan boomslang (SAIMR Boomslang Snakebite Antiserum SAVP). Tidak ada antivenom yang tersedia untuk gigitan ular / burung ranting (Thelotornis).

Pembengkakan lokal sedang sampai ditandai, terkait dengan neurotoksisitas

Ular yang bertanggung jawab atas sindrom ini meliputi:

• berg adder (Bitis atropos) (Gambar 24)

• penambah kecil / kerdil lainnya (adder berliku samping - B. peringueyi dan penggali gunung gurun - B. xeropaga).

Lihat Gambar 25 dan Tabel 1 untuk distribusi dan klasifikasi penambah kurcaci.

Fosfolipase A2 neurotoksin bertanggung jawab atas efek racun dari venom ular ini. Neurotoksin bertindak secara presynaptis, awalnya melepaskan asetilkolin, diikuti oleh gangguan atau pemblokiran pelepasannya.

Gambaran klinis

Setelah sakit awal dan perkembangan pembengkakan lokal, parestesi lidah dan bibir, pengaburan penglihatan dan hilangnya indra penciuman (anosmia) dan rasa, dan disfagia berkembang, seringkali dalam waktu 2 - 3 jam setelah gigitan. Oftalmoplegia eksternal dan internal ditandai oleh ptosis, pupil yang melebar dan kehilangan pergerakan mata dan akomodasi. Kelemahan otot dan gagal napas adalah komplikasi yang umum terjadi (pada> 50% kasus) dan biasanya berkembang terlambat (6 - 36 jam setelah gigitan), seringkali pada tahap ketika tidak diantisipasi atau diperkirakan.

Hiponatremia, yang disebabkan oleh racun mirip hormon natriuretik yang ada dalam racun, juga merupakan komplikasi yang sering terjadi. Biasanya berkembang terlambat (24 - 36 jam pasca gigitan). Jika tidak terdeteksi, hal ini dapat menyebabkan konvulsi tak terduga (lihat lebih jauh di bawah manajemen).

Ophthalmoplegia dan anosmia mungkin memerlukan waktu yang cukup lama untuk menyelesaikannya (berminggu-minggu sampai berbulan-bulan).

Efek lokal termasuk pembengkakan lokal moderat sampai ditandai. Pembengkakan mungkin melibatkan lebih dari setengah anggota badan yang digigit. Terik dan nekrosis bisa berkembang di daerah tempat gigitan. Perubahan kulit sitotoksik yang ekstensif dan sindrom kompartemen tidak diharapkan terjadi.

Gambar 26 menunjukkan ptosis setelah gigitan berg adder dan Gambar 27 gigitan berg adder menunjukkan pembengkakan lokal. Gambar 28 menunjukkan perubahan nekrotik lokal setelah gigitan berg adder.

Investigasi khusus yang disarankan harus mencakup urinalisis, urea dan elektrolit, hitung darah penuh, saturasi oksigen dan tes fungsi pernafasan lainnya. Perhatian khusus harus diberikan pada kadar natrium plasma. Tingkat natrium harus dicatat secara berkala sampai hiponatremia dicatat atau sampai saat hiponatremia telah dikeluarkan, misalnya pada 4 hari setelah envenoming.

Antivenom tidak tersedia untuk berg adder dan gigitan kurcaci lainnya.

Bengkak ringan sampai sedang, dengan gejala sistemik yang tidak berarti atau tidak ada

Ular yang bertanggung jawab atas sindrom ini meliputi:

• night adder (Causus rhombeatus) (Gambar 29)

• menggali asp (Atractaspis bibronii) (Gambar 30)

• Natal ular hitam (Macrelaps microlepidotus)

• beberapa penambah kurcaci, misalnya penanda bertanduk (Bitis caudalis) (Gambar 31).

Gambar 32 dan 33 menunjukkan distribusi penambah malam, semak belukar dan ular hitam Natal.

Gambaran klinis

Gejala dan tanda terkait meliputi nyeri lokal, limfadenopati regional dan demam. Bengkak jarang melibatkan lebih dari setengah anggota badan yang digigit. Blistering dan nekrosis bisa berkembang di tempat gigitan. Perubahan kulit sitotoksik yang ekstensif dan sindrom kompartemen tidak diharapkan terjadi. Gigitan ular natal Natal dikatakan telah mengakibatkan keruntuhan dan hilangnya kesadaran.

Envenoming minor dengan meludahkan kobra dan penambah utama harus dipertimbangkan dalam diagnosis banding pada kasus dimana ular belum diidentifikasi. Investigasi khusus harus mencakup urinalisis dan hitung darah penuh.

Antivenom tidak tersedia untuk gigitan ular yang disebutkan di atas.

Untuk informasi berkenaan dengan envenoming oleh ular berbisa yang kurang diketahui atau yang tidak terdokumentasi dengan baik (misalnya garter dan ular karang), berkonsultasilah dengan Tabel 1.

Pengelolaan gigitan ular

Pertolongan pertama dan manajemen umum

• Saat melembagakan prosedur pertolongan pertama, atur transportasi untuk membawa pasien ke fasilitas medis sesegera mungkin. Gunakan ponsel dan bentuk komunikasi lainnya untuk meminta bantuan. Waspada fasilitas medis atau dokter menjelang kedatangan.

• Yakinkan korban, siapa yang takut.

• Hapus pakaian, cincin, gelang, gelang, sepatu, dll dari cabang / cabang yang digigit.

• Imobilisasi seluruh pasien.

• Hindari banyak perawatan rutin pertolongan pertama yang berbahaya dan membuang-buang waktu seperti kauterisasi, sayatan lokal atau eksisi, tato, pemotongan amputasi profilaksis langsung dari digit yang digigit, suction melalui pompa mulut atau vakum atau aparatus bekas 'bekas-dendam', penanaman bahan kimia senyawa seperti kalium permanganat, aplikasi bensin, bungkus es, 'batu ular' dan sengatan listrik. Tindakan di atas dikontraindikasikan karena berpotensi membahayakan dan tidak ada manfaat yang terbukti.

• Pada dugaan cobotoxic kobra atau gigitan mamba, terutama jika pasien jauh dari bantuan medis, oleskan perban krep ketat ke atas dan proksimal ke tempat gigitan. Prosedur ini bisa mengurangi distribusi cepat racunnya. Hindari krep atau pembalut lainnya dalam semua gigitan sitotoksik.

• Teknik 'immobilisasi tekanan' klasik menuntut peralatan dan pelatihan khusus dan dianggap tidak praktis untuk penggunaan umum di Afrika Selatan.

• Aturniquet arteri yang ketat seharusnya TIDAK PERNAH digunakan! Bahaya tourniquets meliputi perkembangan iskemia dan gangren jika dioleskan lebih dari sekitar 1 ½ jam.

• Karena diagnosis spesies penting, ular yang mati harus dibawa ke rumah sakit. Namun, jika ular masih besar, jangan berisiko gigitan lebih jauh.

• Pada gigitan ular yang diduga neurotoxic, pasien harus dinilai secara teratur (misalnya setiap 10 - 15 menit) untuk pengembangan komplikasi neurotoksisitas.

• Resusitasi kardiopulmoner (CPR) mungkin diperlukan. Ini mencakup pembersihan jalan napas, pemberian oksigen dengan masker wajah atau kateter hidung, dan pembentukan akses intravena. Jika pasien tidak responsif dan tidak ada gerakan pernapasan yang terdeteksi, mulailah CPR. Jika terjadi gangguan / kegagalan pernapasan: bersihkan saluran napas, angkat dagu, berikan oksigen dengan masker wajah atau kateter hidung dengan atau tanpa ventilasi dibantu dan pertimbangkan kebutuhan akan intubasi endotrakeal. Terkejut, pasien hipotensi harus diberi cairan intravena. Agen pengatur, seperti dopamine atau phenylephrine mungkin perlu diberikan.

• Berikan analgesia melalui mulut jika diperlukan: parasetamol (acetaminophen) atau kombinasi parasetamol / kodein lebih diutamakan. Aspirin dan zat antiinflamasi non steroid lainnya harus dihindari pada pasien dengan gangguan hemostatik. Bila menggunakan opioid parenteral pada gigitan ular neurotoksik, fungsi pernafasan harus dipantau secara ketat.

• Pada kasus gigitan berg adder, hiponatremia tidak boleh diobati dengan cara pembatasan cairan, melainkan dengan pemberian garam hipertonik yang dititrasi. Dalam hal ini, pemberian garam normal dapat berguna sebagai alat untuk memenuhi kebutuhan cairan dan garam sebagian.

• Dalam kasus dimana ular belum diidentifikasi, direkomendasikan agar pasien tanpa gejala dirawat di fasilitas medis untuk pengamatan selama 12 - 24 jam.

Antivenom perawatan

Dua antiresoms gigitan ular tersedia:

• Antivenom polivalen (SAIMR Polyvalent Snakebite Antiserum SAVP) diberikan dalam 10 ml ampul. Venom dari ular berikut digunakan sebagai antigen dalam pembuatan antivalom polivalen: puff adder, gaboon adder, rinkhals, green mamba, mamba Jameson, black mamba, kobra hutan, cobra hutan, cobra moncong dan Mozambique yang meludah kobra. Antivenom polivalen tidak efektif DAN TIDAK HARUS DIGUNAKAN dalam pengobatan gigitan yang disebabkan oleh penambah berg, penambah kerdil lainnya, penambah malam, aspal buram dan ular berbulu belakang (boomslang dan ular anggur).

• Boomslang antivenom (SAIMR Boomslang Snakebite Antiserum SAVP) diberikan dalam 10 ml ampul. Hal ini efektif melawan racun boomslang, tapi tidak melawan racun ular berbisa (burung ranting ular).

Antivenom menetralisir sejumlah racun. Karena ular menyuntikkan jumlah racun yang sama ke dalam orang dewasa dan anak-anak, dosis / volume antivenom yang sama harus diberikan pada anak-anak seperti pada orang dewasa.

Antivenom tidak selalu diperlukan: beberapa pasien digigit ular berbisa dan 10 - 50% dari mereka yang digigit ular berbisa tidak envenomed (disebut 'gigitan kering').

Indikasi untuk perawatan antivenom setelah gigitan ular Afrika Selatan:

• neurotoksisitas

• Parameter penggumpalan darah abnormal, darah yang tidak dapat diobati dan / atau perdarahan sistemik spontan

• Pembengkakan cepat dan / atau ekstensif yang melibatkan lebih dari setengah anggota badan yang digigit dalam beberapa jam setelah gigitan

• Kelainan kardiovaskular seperti hipotensi, syok dan aritmia jantung.

Tindakan pencegahan

Pengujian kulit untuk sensitivitas tidak disarankan, karena tidak dapat diandalkan dan hanya menunda pemberian antivenom yang mendesak.

Pemberian antivenom dapat dikaitkan dengan reaksi merugikan yang mengancam jiwa (anafilaksis), reaksi pirogenik (demam), atau penyakit kompleks imun akhir (serum sickness). Sebagian besar reaksi alergi akut / parah terjadi pada jam pertama setelah pemberian antivenom dan hanya jumlah yang dapat diabaikan terjadi lebih dari 6 jam setelah pemberian.

Tidak ada kontraindikasi mutlak untuk pengobatan antivenom saat pasien mengalami envenoming sistemik yang mengancam jiwa. Namun, pasien dengan riwayat atopik dan mereka yang memiliki riwayat reaksi sebelumnya terhadap antisera kuda memiliki peningkatan risiko reaksi antivenom yang parah. Dalam kasus ini, pretreatment dengan adrenalin subkutan, 0,25 ml larutan 1: 1 000 (250 μg) pada orang dewasa dibenarkan untuk mencegah atau mengurangi reaksinya. Pada anak-anak dosis adrenalin adalah 0,01 mg / kg. Beberapa ahli menganjurkan adrenalin profilaksis pada semua pasien.

Premedikasi dengan antihistamin dapat mengurangi reaksi alergi ringan namun tidak akan mencegah reaksi alergi / anafilaktoid yang serius. Hidrokortison memerlukan beberapa jam untuk bertindak dan tidak efektif sebagai agen profilaksis terhadap reaksi akut.

Infus antirom yang lambat, daripada pemberian bolus, dianjurkan sebagai metode untuk mengurangi reaksi antivenom yang serius (perhatikan kelebihan cairan akut pada anak-anak).

Dosis dan metode administrasi

Anak-anak harus diberi dosis antivenom yang sama dengan orang dewasa. Antivenom harus diberikan sesegera mungkin begitu tanda-tanda envenoming lokal sistemik atau parah terbukti. Meskipun antivenom polivalen lebih efektif bila diberikan lebih awal (dalam 6 jam setelah gigitan) dapat diberikan hingga 24 - 48 jam atau lambat dalam envenomations serius - tidak ada kata terlambat untuk memberi antivenom.

Antivenom paling efektif bila diberikan secara intravena. Ini harus diencerkan dengan cairan isotonik dan diinfuskan selama 30 - 60 menit (dalam kebanyakan kasus, wadah volume 200 ml cukup). Injeksi intramuskular tidak disarankan. Jangan menyuntikkan antivenom ke dalam atau sekitar luka.

Dosis intravena yang direkomendasikan dari antivenom polivalen pada gigitan ular sitotoksik serius (puff adder, gaboon adder) adalah 50 - 100 ml (5 - 10 ampul). Pada gigitan ular neurotoksik (mambas, kram saraf neurotoksik) dosis yang dianjurkan adalah 80 - 120 ml (sampai 200 ml pada kasus gigitan mamba yang parah). Dosis lanjutan kadang-kadang diperlukan dalam gigitan mamba hitam.

Dosis yang dianjurkan dari antigen boomslang adalah 20 ml (2 ampul) secara intravena dalam cairan isotonik yang diberikan lebih dari 30 menit. Dosis follow up 10 ml terkadang diperlukan.

Respon terhadap pengobatan antivenom

Tanda neurotoksik membaik perlahan setelah beberapa jam (2 - 6 jam), seringkali tidak meyakinkan. Harus ditekankan bahwa pemberian antivenom polivalen pada fase akut dari enkapsulasi neurotoksik biasanya tidak mencegah perkembangan efek neurotoksik, terutama kelumpuhan pernafasan, dan akibatnya pasien tidak akan bertahan tanpa dukungan hidup. Dukungan pernafasan adalah satu-satunya modalitas pengobatan yang menyelamatkan jiwa dalam ingatan neurotoxic envenoming. Namun, pemberian infektivitas dosis antiretroviral secara intravena akan mengurangi waktu kelumpuhan otot dan pemulihan. Demikian pula, dalam enkapsulasi sitotoksik, Pemberian antivenom polivalen tidak akan membalik tetapi bisa membatasi kerusakan jaringan lebih lanjut. Namun, di boomslang menggigit efek haemostatic dengan cepat dibalikkan oleh booming kenang-kenangan kapanpun setelah gigitan.

Pengobatan reaksi antivenom

Reaksi serius awal bisa dimulai 3 - 60 menit setelah memulai pemberian intravena. Adrenalin (epinefrin) 0,1% (1: 1 000) harus diberikan secara intramuskular dalam dosis 0,5 - 1,0 ml untuk orang dewasa dan 0,01 mg / kg untuk anak-anak. Ini harus diikuti dengan injeksi intravena antagonis H1 (antihistamin) yang lambat seperti prometazin pada dosis 25 - 50 mg pada orang dewasa. Hal ini dikontraindikasikan pada anak-anak berusia 
<2 tahun. Pada anak-anak 5 - 10 tahun dosis prometazin adalah 6,25-12,5 mg dan pada anak-anak 10 - 16 tahun 12,5 - 25 mg (atau 0,125 - 0,5 mg / kg).

Reaksi terlambat (serum sickness type) terjadi 5 - 24 (rata-rata 7) hari setelah perawatan. Ini muncul dengan gatal, urtikaria, demam, artralgia, pembengkakan periartikular, proteinuria dan kadang gejala neurologis. Antihistamin digunakan untuk serangan ringan, namun pada kasus yang parah, prednisolon jangka pendek harus diberikan.

Pengobatan tambahan

Meskipun sebagian besar efek lokal dari gigitan ular berasal dari aktivitas sitolitik dan kegiatan racun lainnya, gigitan tersebut dapat menyebabkan bakteri patogen. Risiko infeksi lokal sangat meningkat jika luka itu menorehkan dengan instrumen yang tidak steril atau dirusak dengan cara lain. Luka harus dibersihkan dengan antiseptik. Blister dan tegang bullae harus disedot hanya jika pecah tampaknya sudah dekat. Anggota badan yang digigit ular harus dirawat dalam posisi yang paling nyaman namun sebaiknya tidak ditinggikan secara berlebihan jika terjadi pembengkakan atau kecurigaan sindrom intrakompartmental yang baru terjadi, karena ini meningkatkan risiko iskemia. Jaringan redup, serosanguinous discharge dan nanah harus dikultur dan pasien diobati dengan antimikroba yang sesuai.

Saran bedah ahli harus dicari jika memungkinkan.

Sindrom kompartemen

Ini jarang terjadi dan terlalu didiagnosis, namun memerlukan perhatian segera. Gambaran klinis anggota badan yang digigit ular sering menunjukkan adanya sindrom kompartemen. Mungkin ada rasa sakit yang parah, pembengkakan yang tegang, kulit sianosis dingin, nyeri pada peregangan pasif otot dan denyut nampak tidak ada. Namun, penampilan ini biasanya menyesatkan. Bila tekanan intracompartmental (jaringan) diukur secara langsung (misalnya dengan monitor Stryker) biasanya ditemukan berada di bawah ambang bahaya nekrosis iskemik pada otot intrakompartmental. Jika perawatan konservatif gagal, fasciotomi full-length harus dilakukan, menyediakan tidak ada koagulopati atau trombositopenia berat. Perlu disebutkan bahwa penelitian pada hewan telah menunjukkan bahwa fasciotomi tidak efektif dalam menyelamatkan otot yang envenomed. Asalkan pemberian antivenom yang adekuat diberikan sesegera mungkin setelah menggigit, fasciotomi jarang sekali dibutuhkan.

Jaringan nekrotik harus didiskriminasikan oleh ahli bedah. Grafik kulit mungkin diperlukan.

Kelainan hemostatik

Pemulihan fungsi hemostatik normal dapat dipercepat dengan memberikan seluruh darah segar, plasma beku segar, kriopresipitat atau konsentrat trombosit.

NB: Agen Heparin dan antifibrinolitik tidak boleh digunakan pada pasien gigitan ular. Heparin tidak menghambat trombin abnormal yang dihasilkan oleh venom ular dan membesar-besarkan, kadang-kadang fatal, gangguan hemostatik.

Gagal ginjal akut dapat disebabkan oleh perdarahan, iskemia akibat hipotensi, efek kelainan pembekuan darah, vasokonstriksi ginjal, nefropati pigmen yang disebabkan oleh haemoglobinuria atau mioglobinuria, nephrotoxicity langsung dan kompleks imunomer glomerulonefritis yang disebabkan oleh reaksi serum sickness terhadap antivenom. Jika output urin turun di bawah 400 ml dalam 24 jam, tekanan vena sentral harus dipantau dan kateter uretra dimasukkan. Rehidrasi hati-hati dengan cairan isotonik dapat diikuti dengan dosis tinggi furosemid. Jika tindakan ini gagal, dialisis dapat diindikasikan.

Terapi antikolinesterase sebagai pilihan untuk gigitan kobra neurotoxic

Blokade Neuromusclar oleh neurotoksin pasca-sinaptik (misalnya racun kobra neurotoksik) sebagian dapat diatasi dengan penggunaan obat antikolinesterase. Meskipun antikolinesterase dapat membantu dalam pengelolaan, ini seharusnya tidak menggantikan terapi antivenom dan juga tidak diprioritaskan karena dukungan pernafasan. Ini mungkin bermanfaat bagi pasien alergi terhadap antivenom. Terapi anticholinesterase, bagaimanapun, tidak direkomendasikan dalam gigitan ular dengan neurotoxin presinaptik, seperti mamba atau penanda neurotoksik. Dosis uji edrophonium untuk menilai apakah terapi antikolinesterase dapat bermanfaat umumnya direkomendasikan. Namun, edrophonium tidak tersedia di Afrika Selatan. Oleh karena itu, Neostigmin digunakan di seluruh tubuh.

Pemberian antikolinesterase memerlukan pemberian bersama obat antikolinergik untuk memblokir efek muskarinik yang berpotensi serius, seperti bradikardia, bronkospasme dan peningkatan sekresi. Dua obat antikolinergik tersedia untuk tujuan ini, yaitu atropin dan glikoprata. Glycopyrrolate adalah antikolinergik yang disukai. Ini mendapatkan popularitas karena menghasilkan takikardia yang kurang dari pada atropin, ini adalah antisialagog yang jauh lebih manjur dan tidak menembus sawar darah otak. Perlu dicatat bahwa pembalikan blokade sulit terjadi bersamaan dengan asidosis respiratorik.

Regimen dosis rata-rata yang direkomendasikan untuk pembalikan blokade neuromuskular non-depolarisasi pada orang dewasa adalah neostigmin 2,5 mg dan glikopirat 0,6 mg (atau atropin 1 mg) yang diberikan bersamaan sebagai bolus. Regimen dosis yang sama dianjurkan untuk mengatasi blokade postsynaptic akibat gigitan ular. Umumnya dianjurkan agar dosis glikoprotein (Robinul) menjadi 0,2 mg (1 ml) untuk masing-masing 1,0 mg neostigmin. Pada anak-anak, jadwal pemberian dosis neostigmin untuk pembalikan blokade neuromuskular non-depolarisasi adalah 0,03 - 0,07 mg / kg, maksimum 2,5 mg). Dosis rata-rata glikoprotein dengan neostigmin adalah 0,010 - 0,015 mg / kg. (Dosis atropin yang direkomendasikan dengan neostigmin pada anak-anak adalah 0,02 - 0,03 mg / kg.) Pasien yang merespons secara meyakinkan dengan menunjukkan peningkatan kekuatan otot dan / atau perbaikan ptosis dapat dipertahankan pada neostigmin 0,5 - 2,5 mg setiap 1 - 3 jam secara intravena. sampai 10 mg per 24 jam untuk orang dewasa atau 0,01 - 0,04 mg / kg setiap 2 - 4 jam untuk anak-anak. Sekali lagi, dosis glycopyrrolate harus 0,2 mg (1 ml) untuk masing-masing 1,0 mg neostigmin. ) Pasien yang merespons secara meyakinkan dengan menunjukkan peningkatan kekuatan otot dan / atau perbaikan ptosis dapat dipertahankan pada neostigmin 0,5 - 2,5 mg setiap 1 - 3 jam secara intravena sampai 10 mg per 24 jam untuk orang dewasa atau 0,01 - 0,04 mg / kg setiap 2 - 4 jam untuk anak-anak. Sekali lagi, dosis glycopyrrolate harus 0,2 mg (1 ml) untuk masing-masing 1,0 mg neostigmin. ) Pasien yang merespons secara meyakinkan dengan menunjukkan peningkatan kekuatan otot dan / atau perbaikan ptosis dapat dipertahankan pada neostigmin 0,5 - 2,5 mg setiap 1 - 3 jam secara intravena sampai 10 mg per 24 jam untuk orang dewasa atau 0,01 - 0,04 mg / kg setiap 2 - 4 jam untuk anak-anak. Sekali lagi, dosis glycopyrrolate harus 0,2 mg (1 ml) untuk masing-masing 1,0 mg neostigmin.

Ulkus ular ophthalmia

Racun ular ophthalmia disebabkan saat racun meludah ke mata. Spesies elapid yang meludah di Afrika bagian selatan (Naja mossambica, N. nigricollis, N. nigricincta dan Hemachatus haemachatus) dapat menyebabkan konjungtivitis intens dan erosi kornea bulus, dipersulit oleh infeksi sekunder, uveitis anterior, kekeruhan kornea dan kebutaan permanen.

Pengobatan pertolongan pertama terdiri dari irigasi mata atau membran mukosa yang terkena dampak sesegera mungkin, menggunakan sejumlah besar air atau cairan hambar lainnya yang tersedia seperti susu. Satu aplikasi tetes anestesi lokal untuk mengatasi kelopak mata tertutup rapat (blepharospasm) dapat digunakan untuk memfasilitasi irigasi. Perawatan antivenom topikal atau sistemik tidak boleh diterapkan atau diberikan. Luka kornea dapat dikecualikan dengan pemeriksaan pewarnaan fluorescein / celah lampu. Jika tidak ada lecet, obati dengan salep mata antibiotik dan alas mata. Resolusi harus terjadi dalam waktu 24 - 48 jam. Jika ada erosi kornea, tetes / salep antibiotik, matik dan mata harus diaplikasikan. Ujian lampu slice setiap hari dianjurkan sampai tuntas. Dokter mata harus dikonsultasikan dalam semua kasus.

Bacaan lebih lanjut tersedia di www.cmej.org.za

Dibetes melitus diet

Diet Therapy
1. Diet Therapy in General
 Diet therapy is the cornerstone of therapy for all patients with diabetes. Practicing an appropriate diet
improves glycemic control.1,2 (grade A)
2. Individualized Diet Therapy
 Individualized diet therapy according to the lifestyle of each patient is essential for successful
introduction and continuation of the recommended diet therapy and requires, first and foremost, that
each patient be interviewed adequately about his/her dietary habits, such as food preferences and diet
timetables as well as his/her physical activity level. (grade A; consensus)
○ The elderly are often associated with disturbance of taste, smell, and mastication, reduced secretion of
saliva and gastric acid, and impaired renal and hepatic function, which leads to malnutrition and
sarcopenia. Therefore, it is required that diet therapy for the elderly be so formulated as to avoid the risk
of malnutrition.
3. Diet Instructions by Registered Dietitians
 In clinical practice, diet instructions involving a registered dietitian are useful for glycemic control.3
(grade B)
 The Food Exchange Lists, edited by the Japan Diabetes Society, is commonly used for diet instructions.
However, if it is difficult for patients to understand the Food Exchange Lists, actual food products or food
models may be used to give instructions. (grade B; consensus)
4. Determination of the Amount of Energy Intake
● The amount of energy intake is to be determined by a physician, with consideration given to his/her
glucose levels, blood pressure, serum lipid levels, height, body weight, age, sex, complications, and energy
expenditure (physical activity), as well as the amount of prior food intake. It must be also determined
individually to meet disease conditions of each patient (e.g., setting a lower target for energy intake for
obese or elderly patients). (grade A; consensus)
Equations used for calculation of energy intake:
Amount of energy intake = ideal body weight × physical activity level
Ideal body weight (kg) = [height (m)]2 × 22
Physical activity level (kcal/kg/ideal body weight)
25-30: low-intensity exercise (e.g., jobs involving deskwork)
30-35: moderate-intensity exercise (e.g., jobs involving standing work)
 35: high-intensity exercise (e.g., jobs involving heavy physical work)
5. Composition of Macronutrients
 In formulating a diet for patients with diabetes, it is to be ensured that carbohydrates account for 50-60%
of the total energy4, while proteins account for 1.0 to 1.2 g/kg/ideal body weight, with the rest of the
energy accounted for by fats. (grade A)
○ Carbohydrates: Given that there is a paucity of evidence as to the intake of carbohydrates in Japan and
there is no consensus as to the lower normal limits for carbohydrate intake, it is desirable that
carbohydrates not more than 60% of the total energy intake; that the intake of sweets, jams or soft drinks
be minimized as they contain a large amount of sucrose that leads to an elevation of triglyceride levels;
and that the intake of fruit be limited to up to 1 unit (80kcal)/day, given that fruits currently on markets
often contain a large amount of sugar as a result of selective breeding.
○ Proteins: While there is a paucity of evidence for protein intake, it is common practice to recommend 1.0
to 1.2 g/kg/ideal body weight of proteins. Intake of less animal protein and more plant protein (e.g.,
soybean products) is recommended to prevent atherosclerosis.5 Protein-restricted diet is recommended
for patients with diabetic nephropathy.
 Saturated and polyunsaturated fats: It is recommended that saturated and polyunsaturated fats account
for not more than 7% and 10% of the total energy intake, respectively. (grade B; consensus)
 n-3 polyunsaturated fatty acids (e.g., eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) which
abound in fish are shown to be effective in lowering glucose and triglyceride levels.6,7
6. Salt Intake
 Excessive salt intake may lead to the onset of vascular diseases through elevation of blood pressure as
well as to an increase in appetite. Therefore, salt intake should generally be limited, and restricted to 6
g/day in patients with diabetes and hypertension and in those with overt nephropathy or more severe
disease. (grade B; consensus)
7. Dietary Fiber Intake
 Intake of dietary fiber (20 to 25 g/day) is shown to be effective in improving glycemic control as well as in
lowering serum lipid levels (cholesterol and triglycerides).8 (grade B)
 Daily intake of 350 g or more of vegetables should be targeted. During meals, taking vegetables first helps
to reduce postprandial glucose increases, HbA1c values, and body weight.9
8. Intake of Varied Foodstuffs
 To avoid vitamin or mineral deficiency, it is to be ensured that patients take as many kinds of food items
as possible. (grade B; consensus) 

dietary guidelines dm 2 pdf

Praktik diet dm sehari hari pdf

References
1. United Kingdom Prospective Diabetes Study (UKPDS) Group. UK Prospective Diabetes Study 7. Response
of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients. Metabolism
1990;39:905-912. (level 3)
2. Wing RR, Blair EH, Bononi P, et al. Caloric restriction per se is a significant factor in improvements in
glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care
1994;17:30-36. (level 1)
3. Kulkarni K, Castle G, Gregory R, et al. Nutrition Practice Guidelines for Type 1 Diabetes Mellitus positively
affect dietitian practices and patient outcomes. The Diabetes Care and Education Dietetic Practice Group. J
Am Diet Assoc 1998;98:62-70/quiz 72-74. (level 3)
4. Anderson JW, Randles KM, Kendall CW, et al. Carbohydrate and fiber recommendations for individuals
with diabetes: a quantitative assessment and meta-analysis of the evidence. J Am Coll Nutr 2004;23:5-17.
(level 1)
5. Fung TT, van Dam RM, Hankinson SE et al: Low-carbohydrate diet and all-cause and cause specific
mortality: two cohort studies. Ann Intern Med 153: 289-298, 2010. (level 2)
6. Garg A. High-monounsaturated-fat diets for patients with diabetes mellitus: a meta-analysis. Am J Clin Nutr
1998;67(Suppl):577S-582S. (level 1)
7. Friedberg CE, Janssen MJ, Heine RJ, et al. Fish oil and glycemic control in diabetes: a meta-analysis.
Diabetes Care 1998;21:494-500. (level 1)
8. Chandalia M, Garg A, Lutjohann D et al: Beneficial effects of higher dietary fiber intake in patients with
type 2 diabetes mellitus. N Engl J Med 342:1392-1398, 2000. (level 1)
9. Imai S, Matsuda M, Hasegawa G, et al. A simple meal plan of “eating vegetables before carbohydrates” was
more effective for achieving glycemic control than an exchange-based meal plan in Japanese patients with
type 2 diabetes. Asia Pac J Clin Nutr 2011;20:161-168. (level 3) D I

Diabetes melitus: koas ini raup lebih 0,5 milyar dari korea selatan

Dr priyo begitu panggilannya, setelah beberapa bulan jadi koas rela cuti untuk melakukan penelitian yang di danai dari korea selatan lebih dari 0,5 milyar.
Mahasiswa salah satu universitas ternama di Yogyakarta ini mendapat tawaran mengiyurkan mengenai salah satu tanaman herbal yang tersebar luas di indonesia. Tanaman kelor yang di telitinya menarik perhatian dari kedutaan Korea Selatan yang langsung di persentasikan di Korea. Bersama timnya berangakat ke Korea mempersentasikan proposal penelitian tentang infusan daun kelor. Awalnya pihak korea selatan menawarkan 0,5 milyar, namun disepakati sekitar 700 juta setelah negosiasi. Penelitian ini cukup banyak melibatkan pakar kedokteran mengingat permintaan pihak korea selatan yang menginginkan perluasan manfaat daun kelor untuk gym atau massa otot. Penelitian yang menggunakan peralatan yang rumit inipun terlaksana walau sempat istirahat beberapa minggu untuk menghilangkan kejenuhan yang mengharuskan timnya berlibur ke singapura dan negara sekitarnya. Setelah beberapa bulan penelitian tentang daun kelor inipun dipresentasikan di korea selatan dengan hasil yang memuaskan. Perkembangan obat herbal diabetes melitus dengan daun kelor menjadi alternatif yang praktis bagi penyandang diabetes karena mudahnya tanaman ini ditemukan. Daun kelor mudah dibudidayakan dalam waktu yang singkat. Daun kelor yang ditanam tidak memerlukan perawatan yang kusus dan cukup dikenal mayarakat sehingga mudah dalam sosialisasi manfaat daun kelor. Ini adalah anugrah alam dari Allah SWT atas kemurahannya, semoga kita bisa mensyukurinya.    

Approved: New Antimicrobial Stewardship Standard

The Joint Commission recently announced a new Medication Management (MM)
standard for hospitals, critical access hospitals, and nursing care centers. Stan￾dard MM.09.01.01 addresses antimicrobial stewardship and becomes effective
January 1, 2017.
Current scientific literature emphasizes the need to reduce the use of inap￾propriate antimicrobials in all health care settings due to antimicrobial resistance.
According to the World Health Organization (WHO): “Antimicrobial resistance
threatens the effective prevention and treatment of an ever-increasing range of
infections caused by bacteria, parasites, viruses and fungi.”1
The Centers for Disease
Control and Prevention (CDC) identified that 20%–50% of all antibiotics pre￾scribed in US acute care hospitals are either unnecessary or inappropriate.2
The
CDC has also stated: “Antibiotics are among the most commonly prescribed medi￾cations in nursing homes. Up to 70% of long-term care facilities’ residents receive
an antibiotic every year.”3
On June 2, 2015, The Joint Commission participated in the White House
Forum on Antibiotic Stewardship. The Joint Commission joined representatives
from more than 150 major health care organizations, food companies, retailers, and
animal health organizations at the forum to express commitment for implementing
changes over the next five years to slow the emergence of antibiotic-resistant bacte￾ria, detect resistant strains, preserve the efficacy of existing antibiotics, and prevent
the spread of resistant infections.4
Subsequently, The Joint Commission developed the antimicrobial steward￾ship standard for hospitals, critical access
hospitals, nursing care centers, ambula￾tory care organizations, and office-based
surgery practices and conducted a field
review in November and December
2015. Prior to and during the field
review, Joint Commission staff conducted
stakeholder calls on the proposed antimi￾crobial stewardship standard with several
governmental and professional organiza￾tions, including the Centers for Medicare & Medicaid Services (CMS), the CDC, and the Society for
Healthcare Epidemiology of America (SHEA).
There was significant support for the antimicrobial
stewardship standard for the hospital, critical access hospital,
and nursing care center accreditation programs. Additionally,
CMS is in the process of developing a Condition(s) of Par￾ticipation (CoP) on antimicrobial stewardship for the hospital
and nursing home settings, which therefore aligns the Joint
Commission’s standard with CMS’s plans for a CoP(s) in this
area. In the meantime, the antimicrobial stewardship standard
for Joint Commission–accredited ambulatory care organiza￾tions and office-based surgery practices is still in development.
The approved antimicrobial stewardship standard and
EPs are shown in the box that begins below and will also be
displayed on The Joint Commission website at http://www.
jointcommission.org/standards_information/prepublication_
standards.aspx. In addition, the requirements will be posted
in the fall 2016 E-dition® update and published in the 2017
Comprehensive Accreditation Manual for the Critical Access
Hospital, Hospital, and Nursing Care Center Accreditation
Programs.
Questions regarding the new antimicrobial stewardship
standard may be directed to Kelly Podgorny, DNP, CPHQ, RN,
project director, Department of Standards and Survey Methods,
The Joint Commission, at kpodgorny@jointcommission.org. P
References
1. World Health Organization. Antimicrobial Resistance. (Updated: Apr
2015.) Accessed May 27, 2016. http://www.who.int/mediacentre/
factsheets/fs194/en/#
2. Centers for Disease Control and Prevention. Core Elements of Hospital
Antibiotic Stewardship Programs. Accessed May 27, 2016. http://www.
cdc.gov/getsmart/healthcare/implementation/core-elements.html
3. Centers for Disease Control and Prevention. Antibiotic Use in Nursing
Homes. Nov 5, 2013. Accessed May 27, 2016. http://www.cdc.gov/
getsmart/healthcare/learn-from-others/factsheets/nursing-homes.html
4. The Joint Commission. Joint Commission Joins White House Effort to
Reduce Antibiotic Overuse. Jt Comm Perspect. 2015 Jul;35(7):4, 11.

Standard MM.09.01.01
The [critical access] hospital has an antimicrobial stewardship
program based on current scientific literature.
Elements of Performance for MM.09.01.01
1. Leaders establish antimicrobial stewardship as an orga￾nizational priority. (See also LD.01.03.01, EP 5)
Note: Examples of leadership commitment to an antimi￾crobial stewardship program are as follows:
l Accountability documents
l Budget plans
l Infection prevention plans
l Performance improvement plans
l Strategic plans
l Using the electronic health record to collect antimi￾crobial stewardship data
2. The [critical access] hospital educates staff and li￾censed independent practitioners involved in antimicro￾bial ordering, dispensing, administration, and monitor￾ing about antimicrobial resistance and antimicrobial
stewardship practices. Education occurs upon hire or
granting of initial privileges and periodically thereafter,
based on organizational need.
3. The [critical access] hospital educates patients, and
their families as needed, regarding the appropriate use
of antimicrobial medications, including antibiotics. (For
more information on patient education, refer to Stan dard PC.02.03.01)
Note: An example of an educational tool that can be
used for patients and families includes the Centers for
Disease Control and Prevention’s Get Smart docu￾ment, “Viruses or Bacteria—What’s got you sick? at
http://www.cdc.gov/getsmart/community/downloads/
getsmart-chart.pdf.
4. The [critical access] hospital has an antimicrobial stew￾ardship multidisciplinary team that includes the follow￾ing members, when available in the setting:
l Infectious disease physician
l Infection preventionist(s)
l Pharmacist(s)
l Practitioner
Note 1: Part-time or consultant staff are acceptable as
members of the antimicrobial stewardship multidisci￾plinary team.
Note 2: Telehealth staff are acceptable as members of
the antimicrobial stewardship multidisciplinary team.
5. D The [critical access] hospital’s antimicrobial steward￾ship program includes the following core elements:
l Leadership commitment: Dedicating necessary hu￾man, financial, and information technology resources.
l Accountability: Appointing a single leader respon￾sible for program outcomes. Experience with suc￾cessful programs shows that a physician leader is
effective.
l Drug expertise: Appointing a single pharmacist leader
responsible for working to improve antibiotic use.
l Action: Implementing recommended actions, such
as systemic evaluation of ongoing treatment need,
after a set period of initial treatment (for example,
“antibiotic time out” after 48 hours).
l Tracking: Monitoring the antimicrobial stewardship
program, which may include information on antibi￾otic prescribing and resistance patterns.
l Reporting: Regularly reporting information on the
antimicrobial stewardship program, which may
include information on antibiotic use and resistance,
to doctors, nurses, and relevant staff.
l Education: Educating practitioners, staff, and
patients on the antimicrobial program, which may
include information about resistance and optimal
prescribing. (See also IC.02.01.01, EP 1 and
NPSG.07.03.01, EP 5)
Note: These core elements were cited from the Centers
for Disease Control and Prevention’s Core Elements of
Hospital Antibiotic Stewardship Programs (http://www.
cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf).
The Joint Commission recommends that organizations
use this document when designing their antimicrobial
stewardship program.
6. D The [critical access] hospital’s antimicrobial steward￾ship program uses organization-approved multidisci￾plinary protocols (for example, policies and procedures).
Note: Examples of protocols are as follows:
l Antibiotic Formulary Restrictions
l Assessment of Appropriateness of Antibiotics for
Community-Acquired Pneumonia
l Assessment of Appropriateness of Antibiotics for
Skin and Soft Tissue Infections
l Assessment of Appropriateness of Antibiotics for
Urinary Tract Infections
l Care of the Patient with Clostridium difficile (c.-diff)
l Guidelines for Antimicrobial Use in Adults
l Guidelines for Antimicrobial Use in Pediatrics
l Plan for Parenteral to Oral Antibiotic Conversion
l Preauthorization Requirements for Specific
Antimicrobials
l Use of Prophylactic Antibiotics
7. D The [critical access] hospital collects, analyzes, and
reports data on its antimicrobial stewardship program.
Note: Examples of topics to collect and analyze data
on may include evaluation of the antimicrobial steward￾ship program, antimicrobial prescribing patterns, and
antimicrobial resistance patterns.
8. D The [critical access] hospital takes action on im￾provement opportunities identified in its antimicrobial
stewardship program. (See also MM.08.01.01, EP 6)

Applicable to Nursing Care Centers
Effective January 1, 2017
Medication Management (MM)
Standard MM.09.01.01
The organization has an antimicrobial stewardship program
based on current scientific literature.
Elements of Performance for MM.09.01.01
1. Leaders establish antimicrobial stewardship as an orga￾nizational priority. (See also LD.01.03.01, EP 5)
Note: Examples of leadership commitment to an antimi￾crobial stewardship program are as follows:
l Accountability documents
l Budget plans
l Infection prevention plans
l Performance improvement plans
l Strategic plans
l Using the electronic health record to collect antimi￾crobial stewardship data
2. The organization educates staff and licensed inde￾pendent practitioners involved in antimicrobial order￾ing, dispensing, administration, and monitoring about
antimicrobial resistance and antimicrobial stewardship
practices. Education occurs upon hire or granting of
initial privileges and periodically thereafter, based on
organizational need.
3. The organization educates residents, and their families
as needed, regarding the appropriate use of antimi￾crobial medications, including antibiotics. (For more
information on patient and resident education, refer to
Standard PC.02.03.01)
Note: An example of an educational tool that can be
used for patients and families includes the Centers for
Disease Control and Prevention’s Get Smart docu￾ment, “Viruses or Bacteria—What’s got you sick? at
http://www.cdc.gov/getsmart/community/downloads/
getsmart-chart.pdf.
4. The organization has an antimicrobial stewardship mul￾tidisciplinary team that includes the following members,
when available in the setting:
l Infectious disease physician
l Infection preventionist(s)
l Pharmacist(s)
l Practitioner
Note 1: Part-time or consultant staff are acceptable as
members of the antimicrobial stewardship multidisci￾plinary team.
Note 2: Telehealth staff are acceptable as members of
the antimicrobial stewardship multidisciplinary team.
5. D The organization’s antimicrobial stewardship pro￾gram includes the following core elements:
l Leadership commitment: Demonstrate support and
commitment to safe and appropriate antibiotic use
in your facility.
l Accountability: Identify physician, nursing, and phar￾macy leads responsible for promoting and oversee￾ing antibiotic stewardship activities in your facility.
l Drug expertise: Establish access to consultant
pharmacists or other individuals with experience or
training in antibiotic stewardship for your facility.
l Action: Implement policy or practice changes to
improve antibiotic use.
l Tracking: Monitor and measure the use of antibiotic
use and at least one outcome from antibiotic use in
your facility.
l Reporting: Regularly reporting information on the
antimicrobial stewardship program, which may
include antibiotic use and resistance, to physicians
and other practitioners, nurses, and relevant staff.
l Education: Provide resources to physicians and
other practitioners, nursing staff, residents, and
families about antibiotic resistance and opportunities
for improving antibiotic use. (See also IC.02.01.01,
EP 1)
Note: These core elements were cited from the Centers
for Disease Control and Prevention’s The Core Ele￾ments of Antibiotic Stewardship for Nursing Homes
(http://www.cdc.gov/longtermcare/prevention/antibiotic￾stewardship.html). The Joint Commission recommends
that nursing care centers use this document when
designing their antimicrobial stewardship program.
6. D The organization’s antimicrobial stewardship pro￾gram uses organization-approved multidisciplinary
protocols (for example, policies and procedures).
Note: Examples of protocols are as follows:
l Antibiotic Formulary Restrictions
l Assessment of Appropriateness of Antibiotics for
Community-Acquired Pneumonia
l Assessment of Appropriateness of Antibiotics for
Skin and Soft Tissue Infections
l Care of the Long Term Care Patient with a Urinary
Tract Infection
l Care of the Patient with Clostridium difficile (c.-diff)
l Facility Guidelines for Antimicrobial Use in Adults
l Plan for Parenteral to Oral Antibiotic Conversion
l Preauthorization Requirements for Specific
Antimicrobials
7. D The organization collects, analyzes, and reports data
on its antimicrobial stewardship program.
Note: Examples of topics to collect and analyze data
on may include evaluation of the antimicrobial steward￾ship program, antimicrobial prescribing patterns, and
antimicrobial resistance patterns.
8. D The organization takes action on improvement op￾portunities identified in its antimicrobial stewardship
program. (See also MM.08.01.01, EP 6)

Ex vivo culture of human atherosclerotic plaques: A model to study immune cells in atherogenesis

Ex vivo culture of human atherosclerotic plaques: A model to study immune
cells in atherogenesis

Abstract
Background and aims: The mechanisms that drive atherosclerotic plaque progression
and destabilization in humans remain largely unknown. Laboratory models are
needed to study these mechanisms under controlled conditions. The aim of this study
was to establish a new ex vivo model of human atherosclerotic plaques that
preserves the main cell types in plaques and the extracellular components in the
context of native cytoarchitecture.
Methods: Atherosclerotic plaques from carotid arteries of 28 patients undergoing
carotid endarterectomy were dissected and cultured. At various time-points, samples
were collected and analysed histologically. After enzymatic digestion, single cells
were analysed with flow cytometry. Moreover, tissue cytokine production was
evaluated.
Results: We optimised the plaque dissection protocol by cutting plaques into circular
segments that we cultured on collagen rafts at the medium–air interface, thus
keeping them well oxygenated. With this technique, the relative presence of T and B
lymphocytes did not change significantly during culture, and the sizes of lymphocyte
subsets remained stable after day 4 of culture. Macrophages, smooth muscle cells,
and fibroblasts with collagen fibres, as well as both T and B lymphocyte subsets and
CD16 natural killer cells, remained largely preserved for 19 days of culture, with a
continuous production of inflammatory cytokines and chemokines.
Conclusions: Our new model of ex vivo human atherosclerotic plaques, which
preserves the main subsets of immune cells in the context of tissue cytoarchitecture,
may be used to investigate important aspects of atherogenesis, in particular, the
functions of immune cells under controlled laboratory conditions.

Introduction
Atherosclerosis and its cardiac and cerebral complications are the leading
causes of death from cardiovascular diseases. For a long time, accumulation of
modified lipoproteins within the arterial wall was considered to be the main cause of
atherosclerotic disease [1]. More recently, however, cells of various types, such as
smooth muscle cells, macrophages, and T cells, have been found to play an
important role in atherosclerotic plaque formation [2]. Moreover, a currently accepted
theory of atherogenesis emphasizes the role of immune system activation caused by
oxidized lipoproteins, which activate endothelial cells (as do other foreign agents
within the vascular wall) [3,4]. It is thought that immune cells are attracted by
chemokines, which are produced by activated endothelial cells, and migrate into the
subendothelium, where they proliferate, leading to atherosclerotic plaque progression
[2,5–7].
The role of immune cells in the growth of plaques has been confirmed in
experimental models on immunodeficient mice, as well as from the presence of
autologous antibodies against oxidized low density lipoproteins in atherosclerotic
plaques [8,9]. In our earlier work, we demonstrated T lymphocyte activation in human
atherosclerotic plaques in comparison with the blood of the same patients [10], thus
providing further evidence for the involvement of the immune system in
atherogenesis.
Despite plentiful evidence for the critical role of the immune system in
atherosclerosis, many important aspects of this phenomenon remain unknown. The
lack of this knowledge is in part due to limitations on access to human atherosclerotic
plaques in vivo, while animal models are often not adequate because of differences

in structures of arterial walls [11,12]. In vitro laboratory-controlled systems are
required for the study of atherosclerotic plaque formation and rupture. Several such
models with cells of only one or two types cultured together have been suggested
[13,14]; however, none of them faithfully reproduces the whole range of intercellular
interactions within human atherosclerotic plaques [15,16].
Here, we describe a new ex vivo model of human atherosclerotic plaques,
which preserves the main cell types of plaques in vivo, together with the general
tissue cytoarchitecture. We think that this model may prove useful for investigation of
immune cell function in atherogenesis and for development of novel therapeutic
approaches to atherosclerosis treatment.
Materials and methods
For a detailed description of the Materials and methods see Supplementary Data.
Patients
We collected atherosclerotic plaques from carotid arteries of 28 patients with
peripheral artery disease, undergoing carotid endarterectomy because of extended
atherosclerosis (19 men and 9 women; mean age ± standard deviation = 65.4 ± 8.5
years). The degree of carotid artery stenosis varied from 65% to 90% (median
90.0%, interquartile range (IQR) 73.8% to 90.0%). Ten patients suffered from
transient ischemic attack or stroke within 5 years before surgery, and more than half
of all plaque specimens (60.7%) were ruptured, as determined from macroscopic
evaluation. All patients’ characteristics are presented in Supplementary Table1.
This protocol was approved by the A.I. Yevdokimov Moscow State University
of Medicine and Dentistry Ethics Committee. All the participants provided written
informed consent.

Tissue processing
Our work was based on the pioneer work of Dr. Hoffman [17,18], who
developed the technique of histoculture that makes possible maintenance of blocks
of mammalian tissues for weeks at the air–liquid interface.
According to the protocol, surgical atherosclerotic plaque samples were
dissected and divided into three parts: one part of the material was fixed in 4%
formaldehyde (Pierce, Thermo Fisher Scientific, Waltham, MA, USA, cat. 28908) and
embedded in paraffin for histological examination, the second part was digested with
an enzymatic cocktail into a single-cell suspension for flow cytometry. The third part
was dissected, placed on a wetted collagen sponge raft (Pfizer, New York, NY, USA,
cat. 0315-08) at the medium–air interface, and cultured. After one day of culture, and
then every 3rd day, culture medium was collected and replaced with fresh medium.
Every 3rd day, several tissue blocks were analysed histologically and by means of
flow cytometry.

Histology
Histology, histochemistry, and immunohistochemistry were performed
according to standard techniques. We focused on several cell types that could not be
properly isolated from plaques by enzymatic treatment and thus were not analysed
with flow cytometry. In particular, we assessed fibroblasts and collagen tissue,
macrophages, and smooth muscle cells, using Masson’s Trichrome staining (Agilent
Technologies, Santa Clara, CA, USA, cat. AR17392-2), antibodies against CD68
(clone KP1, Agilent Technologies) and α-smooth muscle actin (α-SMA) (clone 1A4,
Agilent Technologies), respectively


Statistical analyses

The data obtained in the present study were not normally distributed, according
to the Shapiro-Wilk test, and are presented as medians and IQR. Since distributions
were not normal, for comparison of two independent groups we used the Mann￾Whitney rank test, and for dependent groups we used the Wilcoxon matched pair
test, Friedman ANOVA, and Kendall test. To assess between-group effects, we used
a multiple comparisons rank test. For the age distribution, we made the assumption
of its normality. Statistical analysis was performed with Statistica 10.0 (Statsoft,
Tulsa, OK, USA) and SPSS Statistics 21.0 (IBM, Armonk, NY, USA). Values of p
<0.05 were considered statistically significant.


Results
Histology of ex vivo plaques
Initially, we separated atherosclerotic plaques from normal artery tissue and
dissected them into ~2-mm cubic blocks for culture, similarly to what was
successfully used earlier to culture various human tissues ex vivo [17,19]. However,
analysis of stained histological sections showed that the viability of cultured tissue

blocks of this size decreased over 8–12 days, and cultured blocks contained only ~20
live cells per 100 mg of tissue (Supplementary Fig.3).
We thought that the tissues might be damaged during dissection into small
blocks. Therefore, to diminish tissue injury during preparation, we modified our
protocol and instead of dissecting into small blocks, we sliced tissue into ring-shaped
2-mm thick segments, and with a diameter depending of the carotid artery size (Fig.
1). To verify tissue viability, every 3rd day several dissected segments were analysed
histologically and by means of flow cytometry.
Analysis of histological sections showed that the dissection of plaques into
large circular segments significantly increased cell survival: tissues were preserved
for 19 days. For histological evaluation, tissue segments were stained with
hematoxylin and eosin, Masson’s Trichrome, anti-CD68, and anti-α-SMA antibodies
and their morphology was assessed as described in Materials and methods. We
found that these plaque segments retained their gross morphology and appeared
viable for more than 19 days of culture. In particular, the integrity of the endothelium
and internal elastic membrane, which are most sensitive to the culture conditions,
were preserved over 19 days of culture without a significant increase in the necrotic
core area (Fig. 2).
Furthermore, in 6 plaques, we quantified areas reacting with aniline blue, anti￾CD68, and anti-α-SMA at days 0, 4, 7, and 19 (Fig. 3). We identified macrophages,
fibroblasts, and smooth muscle cells, along with the endothelium, until day 19 of
culture. We found no statistically significant changes (p >0.05) in the fraction of these
cells during the entire culture period (Table 1).

In plaque samples from 16 donors, we assessed tissue viability using flow
cytometry by analysing immune cells extracted from plaque tissue. We compared
flow cytometry results at day 0 with those at days 4, 7, and 19. Towards this goal, we
digested plaque segments with an enzymatic cocktail containing collagenase XI and
desoxyribonuclease I, washed isolated cells, and stained them with live/dead staining
and monoclonal antibodies against CD45, CD3, CD19, CD4, CD8, and CD16. Two
plaques were excluded from the analysis because of a low cellularity at day 0 (lower
than 500 live cells per 100 mg of tissue).
Analysis of tissue at day 0 revealed a median of 6,286.0, IQR [3,172.1–
12,918.9] lymphocytes per 100 mg of plaque tissue. The absolute numbers and
percentages of B lymphocytes among all lymphocytes at day 0 were significantly
lower than those of T lymphocytes (24.6 [7.8–55.3] cells/100 mg vs. 5,694.1
[2,226.7–11,726.6] cells/100 mg; 0.4% [0.1%–0.5%] vs. 89.6% [84.3%–91.2%],
p=0.001). At day 0, among T lymphocytes, the fraction of CD4+CD8- cells was larger
than the fraction of CD4-CD8+ cells (51.6% [43.8%–58.9%] vs. 39.9% [30.0%–
45.1%], p=0.041). The median amount of CD16 NK cells at day 0 was 58.6 [18.7–
360.9] per 100 mg of plaque tissue (Fig. 4). Consecutive flow cytometry after day 0
was performed in plaques from 8 patients, four of which were cultured until day 19.
We showed that,after a decrease during the first 4 days of culture (n=8, 4,125.8
[2,771.4–6,286.0] cells/100 mg at day 0 vs. 2,619.3 [1,360.8–3,712.2] cells/100 mg
at day 4, p=0.036), the amounts of lymphocytes stabilized and did not change
significantly until the 7th day of culture (n=8, 1,249.6 [445.5–3,706.0] cells/100 mg;
p=0.161). A similar pattern was found in T cells, with a stabilization of their amounts
after a reduction during the first 4 days of culture (n=8, 3,546.5 [2,194.2–5,694.1]
cells/100 mg at day 0 vs. 2,123.4 [1,210.5–3,280.1] cells/100 mg at day 4, p=0.036
vs. 949.5 [375.1–2,378.3] cells/100 mg at day 7, p=0.124). In addition, we found no

significant changes in the amounts of B cells during the first days of culture (n=8,
12.2 [5.3–35.3] cells/100 mg at day 0 vs. 5.6 [3.3–37.2] cells/100 mg at day 4 vs.
7.9 [0.0–11.4] cells/100 mg at day 7, p=0.798). Furthermore, both T and B cells were
also preserved in plaque tissues during 19 days of culture, although their ratio
changed slightly because of the decrease in the number of T lymphocytes (n=4,
7,673.4 [3,789.0–14,813.2] cells/100 mg vs. 2,594.5 [1,926.8–7,569.0] cells/100 mg
for T cells, and 25.8 [5.3–57.9] cells/100 mg vs. 31.0 [12.2–91.2] cells/100 mg for B
cells). CD16 NK cells were found at day 19 as well: the median cell count at the last
day of culture constituted 44.9 [21.9–233.0] cells/100 mg (Fig. 5). We presume that
the initial fall in T cell count may originate from the intense effect of tissue dissection,
while the statistically significant decrease in the amounts of B cells and CD16 NK
cells may not have been revealed because of the small size of these cell subsets.
These changes were followed by a subsequent system stabilization. This was also
evident by the lack of significant changes (p=0.417) in the fraction of dead cells,
which even at day 19 remained at the level of on average 11.2% [10.1%–14.6%].
Importantly, the initial drop in T cell count was not accompanied by significant
changes in the fraction of T cells among all lymphocytes (n=8, 89.6% [76.3%–91.2%]
at day 0 vs. 86.2% [81.1%–90.8%] at day 4, p=0.779; vs. 86.0% [77.5%–86.9%] at
day 7, p=0.674) (Fig. 6A). The decrease in T cell numbers during the first days of
culture was predominantly associated with the reduction of the fraction of CD4 T cells
(n=7, 58.0% [43.8%–63.6%] at day 0 vs. 42.0% [31.4%–49.2%] at day 4, p=0.018;
vs. 40.8% [21.6%–48.7%] at day 7, p=0.018), accompanied by a minor rise in the
fraction of CD8 T cells (n=7, 36.0% [30.0%–47.5%] at day 0 vs. 45.2% [35.3%–
48.6%] at day 4, p=0.063; vs 44.4% [37.9%–55.1%] at day 7, p=0.018) (Figure 6B).
As a result of these changes, the CD4+CD8-/CD4-CD8+ ratio decreased slightly
during culture. As of the 19th day of culture, the fraction of CD4 T cells was reduced

with a concurrent increase in the fraction of CD8 T cells (49.7% [40.2%–57.6%] vs.
42.3% [27.8%–51.9%] for CD4 T cells, and 43.6% [36.1%–53.8%] vs. 50.8%
[40.9%–61.9%] for CD8 T cells) (Figure 7). Nevertheless, both CD4 and CD8 T cells
were also preserved in culture for at least 19 days.
Cytokine production by plaques ex vivo
We analysed the concentrations of cytokines and chemokines released by six
cultured plaques and accumulated in the culture medium from day 1 to day 4 and
from day 16 to day 19 when the medium was changed. We found that in our system
plaques produce substantial amounts of interleukin (IL)-1α, IL-6, IL-8, IL-16, IL-18, IL-
21, IL-22, eotaxin, interferon-λ, granulocyte macrophage colony-stimulating factor
(GM-CSF), macrophage-CSF, tumor necrosis factor (TNF)-α, transforming growth
factor (TGF)-β, growth related oncogene (GRO)-α, interferon gamma-inducible
protein-10, monocyte chemoattractant protein-1, monokine induced by gamma
interferon, macrophage inflammatory protein (MIP)-1α, MIP-1β, and RANTES. In
contrast, the concentrations of the other measured cytokines and chemokines were
lower than the detection limit of the Luminex platform for these analytes.
Within the panel of cytokines and chemokines that were detectable in the
culture medium, we found no significant changes during culture in most of the
cytokines, except for IL-16 and several cytokines whose concentration decreased, in
particular IL-8 (n=6, from 25,698.7 [14,817.3–52,553.3] pg/ml on day 4 to 4,273.1
[2,695.6–6,274.2] pg/ml on day 19), and to a lesser extent GM-CSF, TNF-α, and
GRO-α. At the same time, the concentrations of other cytokines (including eotaxin,
TGF-β, and MIP-1β) increased during culture (Supplementary Table 2).


DI