Journal Pre-proof

Adult sedation and analgesia in a resource limited intensive care unit – A Systematic
Review and evidence based guideline

Netsanet Temesgen, Bsazinew Chakol, Tadesse Tamirie, Dinberu Eshetie, Nigussie

Simeneh, Abatneh Feleke

PII: S2049-0801(21)00306-X
DOI: https://doi.org/10.1016/j.amsu.2021.102356
Reference: AMSU 102356

To appear in: Annals of Medicine and Surgery

Received Date: 3 March 2021

Revised Date: 15 April 2021
Accepted Date: 25 April 2021

Please cite this article as: Temesgen N, Chakol B, Tamirie T, Eshetie D, Simeneh N, Feleke A,
Adult sedation and analgesia in a resource limited intensive care unit – A Systematic Review and
evidence based guideline, Annals of Medicine and Surgery (2021), doi: https://doi.org/10.1016/
j.amsu.2021.102356.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.

© 2021 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

Annals of Medicine and Surgery

The following information is required for submission. Please note that failure to respond to these
questions/statements will mean your submission will be returned. If you have nothing to declare
in any of these categories then this should be stated.

Please state any conflicts of interest

All authors must disclose any financial and personal relationships with other people or
organisations that could inappropriately influence (bias) their work. Examples of potential
conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert
testimony, patent applications/registrations, and grants or other funding.

The authors declared that there is no conflict of interest.

of
ro
Please state any sources of funding for your research
All sources of funding should be declared as an acknowledgement at the end of the text. Authors

-p
should declare the role of study sponsors, if any, in the collection, analysis and interpretation of
data; in the writing of the manuscript; and in the decision to submit the manuscript for
re
publication. If the study sponsors had no such involvement, the authors should so state.
lP

No funding is required
na

Ethical Approval
ur

Research studies involving patients require ethical approval. Please state whether approval has
been given, name the relevant ethics committee and the state the reference number for their
Jo

judgement.

Not applicable for ethical approval or Ethical approval is not needed.

Consent
Studies on patients or volunteers require ethics committee approval and fully informed written
consent which should be documented in the paper.

Authors must obtain written and signed consent to publish a case report from the patient (or,
where applicable, the patient's guardian or next of kin) prior to submission. We ask Authors to
confirm as part of the submission process that such consent has been obtained, and the
manuscript must include a statement to this effect in a consent section at the end of the
manuscript, as follows: "Written informed consent was obtained from the patient for publication
of this case report and accompanying images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal on request”.
Patients have a right to privacy. Patients’ and volunteers' names, initials, or hospital numbers
should not be used. Images of patients or volunteers should not be used unless the information is
essential for scientific purposes and explicit permission has been given as part of the consent. If
such consent is made subject to any conditions,the Editor in Chiefmust be made aware of all
such conditions.

Even where consent has been given, identifying details should be omitted if they are not
essential. If identifying characteristics are altered to protect anonymity, such as in genetic
pedigrees, authors should provide assurance that alterations do not distort scientific meaning and
editors should so note.

Not applicable for that

Author contribution

of
Please specify the contribution of each author to the paper, e.g. study concept or design, data

ro
collection, data analysis or interpretation, writing the paper, others, who have contributed in
other ways, should be listed as contributors.

-p
All authors equally contributed to the study concept or design, data searching, data analysis
re
or interpretation, writing the paper.
lP
na

Registration of Research Studies

ur

In accordance with the Declaration of Helsinki 2013, all research involving human participants
has to be registered in a publicly accessible database. Please enter the name of the registry and
Jo

the unique identifying number (UIN) of your study.

You can register any type of research at http://www.researchregistry.com to obtain your UIN if
you have not already registered. This is mandatory for human studies only. Trials and certain
observational research can also be registered elsewhere such as: ClinicalTrials.gov or ISRCTN
or numerous other registries.

1. Name of the registry: http://www.researchregistry.com

2. Unique Identifying number or registration ID: researchregistry 6620

3. Hyperlink to your specific registration (must be publicly accessible and will be

checked: https://www.researchregistry.com/browse-the
registry#home/registrationdetails /603cbc8873c40d001b3a44f1/.
Guarantor

The Guarantor is the one or more people who accept full responsibility for the work and/or the
conduct of the study, had access to the data, and controlled the decision to publish

Mr. Netsanet Temesgen

of
ro
-p
re
lP
na
ur
Jo
Adult Sedation and Analgesia in a Resource Limited Intensive Care
Unit – A Systematic Review and Evidence Based Guideline

Netsanet Temesgen1@,Bsazinew Chakol1, Tadesse Tamirie1, Dinberu Eshetie1, Nigussie

Simeneh2, Abatneh Feleke2

1
Debre Tabor University, College of Health Sciences and Medicine, Department of Anesthesia

2
University of Gondar, College of Medicne and Health Sciences, Department of anesthesia and
Critical Care

of
@
First and Corresponding Author of the Manuscript

ro
-p
@ Corresponding Author’s Email: Netsanettmsgn@gmail.com
PO.Box: 272
re
Ethical approval
lP

Not required
na

Authors' contributions
ur

NT, BC, TT, DE,NS and AB performed literature search, assessment of articles, data extraction,
Jo

data analysis, and manuscript preparation and all the authors have read and approved the

manuscript well.

Acknowledgements

University of Gondar and Debre Tabor University for providing internet Access for our work

All Staff members of Department of Anesthesia from both Universities for their meticulous help

Funding

None
Adult Sedation and Analgesia in a Resource Limited Intensive Care
Unit – A Systematic Review and an Evidence Based Guideline

ABSTRACT
BACKGROUND: Sedation and analgesia are essential in the intensive care unit in order to
promote control of pain, anxiety, prevent loss of materials, accidental extubation and improve the
synchrony of patients with ventilator. However, excess of these medications leads to an
increased morbidity and mortality, and thus demands protocol.

of
METHODS: Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Protocol

ro
have been used to undertake this review. Pub Med, Cochrane Library, and Google Scholar search
engines were used to find up-to-date evidence that helps to draw recommendations and
conclusions.
-p
re
RESULTS: In this Guideline and Systematic Review, we have used 16 Systemic Review and
lP

Meta-Analysis, 3 Evidence-Based Guidelines and 10 RCT Meta-Analysis, 6 Systemic Reviews

na

of Non-randomized Studies, 8 Randomized Clinical Trials, 11 Cohort Studies, 5 Cross-Sectional

Studies and 1 Case Report with their respective study descriptions.
ur

DISCUSSION: Analgesia, which as a sedation basement can reduce sedative use, is key aspect
Jo

of treatment in ICU patients, and we can also conclude that an analgesic sedation regimen can
reduce the occurrence of delirium by reducing sedatives. The aim of this guideline and the
systematic review is to write up and formulate analgesia-based sedation for limited resource
settings.
CONCLUSIONS: Analgesia and sedation are effective in critically ill patients; however, too
much sedation is associated with longer periods of mechanical ventilation and longer duration of
ICU stay. Poorly managed ICU patients have a delirium rate of up to 80%, increased mortality,
longer hospital stays, higher hospital costs and bad long-term outcomes.
Keywords: Sedation and Analgesia in the ICU, ICU Patients, ICU Analgesia, ICU Sedation

1
BACKGROUND

Sedation and analgesia are essential components in the management of all critically ill
patients.(1), Those requiring mechanical ventilation and the main indications for use include to
alleviate patient discomfort, anxiety and agitation, cause amnesia, promote mechanical
ventilation, prevent the displacement of endotracheal tubes, and decrease cell metabolism(2).As
a result, deep sedation was commonly used until a patient was able to breathe without
assistance(3),and developments over the past 30 years, including microprocessor-controlled

of
ventilators that synchronize with patients' own respiratory efforts and new, shorter-acting

ro
sedative and analgesic medications, have drastically changed the way ICU patients are treated
with various treatments (most notably endotracheal intubation and invasive mechanical

-p
ventilation) that are experienced or interpreted.(4).
re
Pain is a common experience for most ICU patients and failing to recognize that pain also
lP

contributes to agitation. It is the most common memory that patients with their ICU stay and
inadequate analgesia and anxiety can precipitate accidental removal of endotracheal tubes or
na

intravascular catheters used to track or administer life-sustaining medications. As a result,

ur

sedatives and analgesics are now becoming one of the most widely used and used medications in
ICU, as equally important ideas have been mentioned that early detection of pain, sedation,
Jo

sedation, and delirium are problems that if undetected and untreated, are distressing to patients
and associated with increased ICU morbidity and mortality(3, 5).

Analgesia and sedation are important components in the treatment of patients in the intensive
care unit (ICU) in order to facilitate management of pain, anxiety and agitation, avoid failure of
equipment, involuntary extubation and enhance the coordination of patients with mechanical
ventilation. However, excess of these drugs contributes to an increase in morbidity and
mortality.(6). Ideal treatment would rely on the implementation of clinical and pharmacological
interventions, driven by scales and guidelines, but the identification and control of pain by
various scholars is difficult in Intensive Care Units (ICUs) due to a variety of conflicting factors
correlated with short-and long-term effects of inadequate pain relief leading to increased adverse
outcomes (2, 7).

2
Sedatives are very common in ICU settings and cannot be thought of as sedative-free ICU
sedations, and these sedatives can alleviate patient distress and stress levels, improve care
delivery and ensure protection, and these sedatives are prescribed to 85 per cent of Intensive
Care Unit (ICU) patients, including intravenous benzodiazepines and propofol are the most
commonly used sedatives(8, 9). However these agents are associated with over-sedation in 40 to
60 % of patients, which can lead to prolonged intubation, delirium and drug-induced
hypotension(4).
Evidences show that newer volatile anesthetic agents are associated with faster extubation times,
improved cardiovascular safety with no end-organ toxicity relative to our normal intravenous

of
agents for short-term critical care sedation. The use of this volatile agent in the ICU is a novel
technique that uses a specialized distribution and scavenging procedure that involves personnel

ro
training and cultural acceptance and sedation protocols and daily sedation interruption does not

-p
appear to vary in comparison to the majority of the findings analyzed(5).
re
Proper sedation is an important component in the care of critically ill patients requiring
mechanical ventilation(10). Deep sedation levels are associated with many negative effects, such
lP

as increased mechanical ventilation time longer ICU stay, delirium, memory disruptions, and
na

higher short-and long-term mortality. In ICU patients, especially those with mechanical
ventilation, the rate of delirium is as high as 80 per cent, in addition to increased mortality,
ur

longer hospital stays, higher hospital costs and poor long-term outcomes are normal(6, 11).
Jo

These and other deleterious effects of deep sedation can be minimized by employing a strategy
of sedation protocols that target lighter sedation levels and the daily interruption of sedative
infusion(12). The results of these techniques were evaluated in two systematic reviews in which
the included research control groups consisted of patients who received "usual treatment for
sedation of patients with mechanical ventilation (6).
Analgesia, which as a sedation basement may reduce the amount of sedatives used is a key and
key component of treatment in the management of ICU patients, and we may therefore conclude
that an analgesic sedation protocol can reduce the incidence of delirium due to a reduction in the
amount of sedatives used(4, 13).
Specific physiological changes that critically ill patients experience can have a direct impact on
the pharmacology of medications, possibly contributing to discrepancies in response between
patients. Objective measures of pain, sedation and anxiety have been validated for use in the ICU

3
for the evaluation and titration of drugs(14, 15). An evidence-based approach for the
administration of these medications will lead to changes in patients' short-and long-term
outcomes. In this guideline, we have reviewed a variety of literature and innovations in the field
of ICU sedation to include an up-to-date perspective on procedures for the treatment of
mechanically ventilated adult ICU patients (16, 17).

of
ro
-p
re
lP
na
ur
Jo

4
METHDODS
This Evidence Based Guideline and Systematic Review is presented by Preferred Reporting
Items Reviews and Meta-Analysis (PRISMA). The level of proof and advice was assessed on the
basis of WHO Evidence of Good Clinical Practice (GCP) and evaluated on the basis of different
assessment checklists to categorize them to level 1 (Meta-analysis and systematic review of
RCTs, Randomized control trials, Evidence based guide lines), level 2 (systematic review of
Well-designed cohort studies) and level 3(Non analytical studies).

The terms ICU sedation and analgesia, 'ICU patients,' 'ICU analgesia' and 'ICU sedation' have
been used in different combinations. After a fair amount of data has been obtained, the

of
assessment and evaluation of the consistency of the research using a different institutional

ro
assessment checklist was used to categorize the evidence.

-p
A total of 44 literatures (16 Met analysis and Systematic reviews, 8 RCTs, 11 Cohort,
re
3Guidelines, 5urveys and 1 case report) were considered and used in this Guideline after they
lP

have been filtered and analyzed accordingly(Fig 1). In this review we have included only full
text articles which have been written in English language and we excluded studies with no
na

defined methods and published before the year 2000GC.

ur

Finally conclusions and recommendations are made by balancing the benefits and drawbacks of
alternative treatment options for sedation and analgesia protocols in the ICU. Best possible
Jo

Conclusions were eventually drawn from the literature on the basis of their strength of evidence
and recommendations for sedation and analgesia in critically ill adult ICU patients (Table 1).

This systematic review and met analysis is registered at www.research registry with ID of 6620
and available at https://www.researchregistry.com/browse-the registry#home/registrationdetails
/603cbc8873c40d001b3a44f1/.

5
 Identificati Records identified via database Additional records found with other
on searching’s (n = 4484) sources (n = 20900)

Records after duplicates and unrelated

ones has been removed (437)
(n =437)
Screening

of
Records excluded
Records screened

ro
(n = 72)
(n = 129)

-p
re
Eligibility

Full-text articles assessed Full-text articles

for eligibility excluded, with reasons (n
lP

(n = 57) = 13, Studies with no

defined methods)
na
ur

Studies included in
Included

qualitative synthesis
Jo

(n = 44)

Fig. 1: PRISMA flow diagram for the searched and used articles.

6
 Table 1: Level of evidence and degrees of recommendations

Level Type of Evidence No of Articles Degrees of Recommendations

Meta analyses, systematic reviews Strongly recommended and directly

of randomized controlled trails applicable
1a 10

1b Systematic review of non- Highly recommended and directly

randomized controlled trails 6 applicable

1c 8 Recommended and applicable

Randomized Controlled

of
Trails(RCTs)

ro
Extrapolated evidence from other
2a Evidence based Guidelines
-p
3 studies
re
lP

Non analytic studies such as 17 Extrapolated Evidence from other

3a Cohort, Surveys, case reports and studies
case series
na
ur
Jo

Good clinical practice, GCP, WHO, 2011

7
 RESULTS

In this Evidence Based Guideline and Systematic Review, we reviewed 16 SR and MA, 8 RCTs
3 evidence-based recommendations, 11 cohort studies, 5 cross-sectional studies and 1 case report
with their respective research details and core findings (Table 2).

Table 2: Summary of articles used for the development of this Systematic review and evidence
based guideline

S Authors and Publication Title of the articles Study Results/Recommendations

N year, Follow up duration Participants
1 Ahlers et.al,2008,90 Comparison of different pain scoring systems 113 Patients In ventilated patients, BPS can only be used in
Days in critically ill patients in a general ICU- A combination with the NRS nurse to assess pain
prospective Cohort levels in the absence of unpleasant stimuli.

of
2 Baron et.al, 2015,365 Managements of Delirium &Agitation-An 284 Studies Sedation shall be performed with a
Days Evidence Based consensus and Guideline combination of hypnotic and analgesics

ro
3 Barr J et.al,2013,210 Prevention and Control of delirium- An 472Studies Early detection and treatment of potential
Days evidence based guideline underlying causes of agitation and anxiety is
important for ICU sedation.
4 Brush et.al,2009,395
Days
-p
Sedation and analgesia for the mechanically
ventilated patient- A Randomized Controlled
92 Patients Mechanically ventilated patients in the
intensive care unit routinely need sedative and
re
Trials analgesic medicine to relieve pain and anxiety.
5 Burry L et.al, 2014,90 Daily sedation interruptions vs. no sedation 9 RCTs and Light sedation is recommended so that patients
lP

Days protocols in the ICU-A systematic review 1282 are responsive and able to communicate and
and met analysis Patients daily interruption of sedation is stimulated.
6 Dale et.al,2014,730 Days Improved analgesia, sedation, and delirium 1483 Protocols for the administration of analgesia,
na

protocol associated with decreased duration Patients sedation and delirium to critically ill,
of delirium and mechanical ventilation-A mechanically ventilated patients have been
prospective Cohort shown to improve outcomes but are not
ur

uniformly used.
7 Deffland et.al,2020,395 Effects of pain, sedation and delirium 1323 Significant improvements in clinical outcome
Days monitoring on clinical and economic Patients can be achieved by implementing effective
Jo

outcome-A retrospective cohort study strategies to optimise pain management, reduce

sedative exposure, and prevent and treat
delirium in ICU patients
8 Devabhakthunis Analgosedation: A paradigm shift in 10 RCTs Analgosedation is an efficient and well-
et.al,2012,363 Days intensive care unit sedation practice-A and 1155 tolerated approach to ICU sedation treatment
systematic review and metanalysis patients with better patient outcomes relative to
sedative-hypnotic approaches.
9 Devlin et.al,2009,Follow Pharmacology of commonly used analgesics 206 Patients who are critically ill and have
up duration is not stated and sedatives in the ICU,benzodiazepines, mechanical ventilation also need sedation and
in the study, propofol, and opioids-A Randomized analgesic treatment to improve patient comfort,
controlled trail promote patient-ventilator coordination and
optimize oxygenation.
10 Ely E Wesley,2003,48 Monitoring sedation status over time in ICU 313 Patients RASS has been shown to be highly accurate
Days patients-Reliability and validity of the and has extended the collection of pivotal
Richmond Agitation-Sedation Scale-A sedation scores that are calculated by patients
prospective cohort study responding to verbal and physical stimulation
by assisting with drugs.
11 Fraser Gl et.al ,2007, Sedation and analgesia in the critically ill 408 The approach to include analgesia-first and
Follow up duration is not adult- A prospective Cohort complemented by sedation-as-needs tends to
stated in the study improve patient outcomes in the ICU.
12 Fraser GL et.al2013, Benzodiazepines Vs non benzodiazepines 6 RCTs and Midazolam for short-term sedation only,

8
 Follow up duration is not therapy- A systematic review and met 1235 lorazepam for long-term sedation, and Propofol
stated in the study analysis patients for patients needing occasional awakening.
13 Hutton B et.al, Sedation strategies in the ICU- A systematic 54 RCTs Protocolized sedation or daily sedation
2016/18,730 Days review and met analysis interruption is recommended.
14 Jareth et.al, 2015, Follow Use of volatile anaesthetics- A randomized 60 Adult Volatile anaesthetics have many
up duration is not stated Controlled Trials ICU Patients pharmacological properties, making it suitable
in the study for extended use in ICU sedation.
15 Keoph SJ et.al, 2015,365 Analgesia based sedation in the ICU- 145 Patients Midazolam and fentanyl were the most
Days Evidence based Guideline commonly used sedation and analgesia
medications during mechanical ventilation.
16 Kim HY et.al, 2017 Volatile sedation in the ICU- A systematic 13RCTs and Inhalational sedation enhances early recovery,
Follow up duration is not review and met analysis 1027 decreased ICU stay and shortens mechanical
stated in the study patients ventilation.
17 Kress JP et.al,2002, Sedation and analgesia in the intensive care 80 Patients Sedation is an important component of the care
Follow up duration is not unit- A Randomized controlled Trail of patients who are mechanically ventilated and
stated in the study critically ill. There is currently a broad range of

of
pharmacological agents available for the
complex needs of this heterogeneous group of

ro
patients undergoing extended sedative
administration.
18 Lavrentieva et.al, 2017, Agitation, Sedation & Analgesia in the ICU- 64 RCTs There is a substantial gap between the

-p
Follow up duration is not A systematic review and met analysis guidelines and clinical practice for the
stated in the study assessment of pain, sedation and delirium and
re
mgt in the ICU setting.
19 Maclaren R Evaluation of empiric versus protocol‐based 72 empiric Compliance with the protocol decreased
et.al,2000,150 Days sedation and analgesia- A prospective cohort and 86 medication prices and increased sedation and
lP

protocol analgesia safety for patients needing long-term

therapy(158) sedation. Protocol-based therapy could have
postponed extubation but did not postpone
na

discharge of the ICU.

20 Martin et.al,2005,180 Practice of sedation and analgesia in German 220 Propofol was the key short-acting agent used
Days intensive care units- A national survey Participants for sedation in ICUs and benzodiazepine
ur

midazolam was used for long-term sedation.

Fentanyl and sufentanil have been used for
Jo

analgesia.
21 Martin et.al,2006, Sedation and analgesia in German intensive 305 The fact that patients were more deeply
Follow up duration is not care units: how is it done in reality? Results Participants sedated than expected by the therapist in all
stated in the study of a patient-based survey of analgesia and phases of sedation may be due to the low use of
sedation- A postal survey sedation scales and clinical procedure protocols
or lack of experience in the use of these
techniques.
22 Meiser et.al,2005 Follow Inhalational anaesthetics in the ICU-Case Two case Most inhalation agents are poor analgesics and
up duration is not stated Report reports analgesia will be required, particularly in
in the study postoperative or trauma patients. Opioids, non-
opioid medications and regional analgesia
strategies can be mixed as needed.
23 Mukhopadhya et.al, Age related inverse doses in the ICU- An 576 Patients Possible interaction between propofol and
2017,850 Days observational Cohort study fentanyl is an essential concern for elderly
patients and Fentanyl can reduce the volume of
the central compartment and thus the clearance
of propofol.
24 Owen GD International Analgesia, Sedation, and 14281 Analgesia and sedation practices have varied
et.al,2019,2195 Days Delirium Practices - A prospective cohort Patients widely across international regions and have
study evolved dramatically over time. Opportunities
for better treatment include increasing control

9
 of delirium, conducting SATs and decreasing
use of sedation, in particular benzodiazepines.
25 Park GC et.al,2001, Balancing sedation and analgesia in the 192 Patients It's challenging to avoid over and under-
Follow up duration is not critically ill –A prospective cohort study sedation. Maintaining a target level of sedation
stated in the study is difficult; patients spend a large proportion of
their ICU remaining at an insufficient level of
sedation.
26 Patanwala et.al,2017,180 Ketamine for analgosedation in the intensive 6RCTs and The use of ketamine may decrease the
Days care unit-A systematic review 6non-RCTs analgesic consumption in the intensive care
and 468 unit. Additional studies are required to better
Patients define the role of ketamine for analgesia.
27 Patel SB et.al, 2009,575 Delirium and sedation in the intensive care 1384 Remifentanil requires less propofol but greater
Days unit (ICU)-A survey of behaviours and Participants discomfort afterwards; equally successful
attitudes healthcare professionals sedation.Propofol faster wake-up, less days of
MV, more efficient sedation.
28 Payen JF et.al,2007,391 Current practices in sedation and analgesia 44 ICUs and Excessively deep sedation and lack of analgesia

of
Days for mechanically ventilated critically ill 1381 during painful operations must be avoided.
patients- A prospective multicenter Cohort Patients Facilitate routine evaluation of pain and

ro
sedation and change the daily dose of drugs
accordingly.
29 Pradilli L et.al, Propofol or benzodiazepines for short-and 35 Sedations are recommended with propofol than

-p
2017,1460 Days long-term sedation in intensive care units- A RCTs,3015 midazolam for short term sedation.
Systematic review and met analysis Patients
re
30 Reade MC et.al,2014, Sedation & delirium in the ICU-A 418 Patients Pain should be handled promptly and
Follow up duration is not prospective Cohort Study effectively, sedative administration should be
stated in the study kept to the minimum required for the comfort
lP

and protection of the patient, and early

mobilization should be achieved wherever
possible.
na

31 Rowe K et.al, 2008, Continuing Education in Anaesthesia, 15 RCTs Over-sedation can increase time on ventilator
Follow up duration is not Critical Care & Pain support, prolong ICU stay, and may Precipitate
stated in the study unnecessary neurological investigations.
ur

32 Rozendaal,et.al,2009, Remifentanil-propofol analgo-sedation 15 Hospitals In patients with predicted short-term duration

Follow up duration is not shortens duration of ventilation and length of and 205 of MV, remifentanil substantially improves
Jo

stated in the study ICU stay compared to a conventional Patients sedation and agitation and decreases weaning
regimen- A randomized controlled trial time. This would lead to a shorter period of
MV and ICU-LOS.
33 Schweickert Strategies to optimize analgesia and sedation 132 Patients Adequate but not excessive sedation in
et.al,2008,185 Days – A randomized Controlled trails critically ill, mechanically ventilated patients is
a complicated operation. The analgesics and
sedatives used in this context are extremely
potent, and drug and metabolism requirements
are unpredictable.
34 Schweickert Early physical and occupational therapy in 104 Patients . Early detection and treatment of potential
et.al,2009,30 Days mechanically ventilated, critically ill underlying causes of agitation and anxiety,
patients- A randomised controlled trial such as pain, delirium, hypoxemia,
hypoglycaemia, hypotension or alcohol
withdrawal and other medications, are very
critical prior to patient sedation.
35 Sessler et.al,2011, Protocolized and target-based sedation and 20 Protocolized target-based sedation and
Follow up duration is not analgesia in the ICU- A systematic review Randomized analgesia are essential to successful sedation
stated in the study and met analysis controlled control. Significant components include the
trials and identification of targets and individual targets,
3588 the use of valid and reliable instruments to
patients assess pain, agitation and sedation, and the

10
 titration of a logically selected combination of
sedatives and analgesics to specified endpoints.
36 Sessler et.al,2008, Patient-focused sedation and analgesia in the 53 Articles Patient-focused treatment includes the selection
Follow up duration is not ICU-A systematic review of drugs ideally suited to patient characteristics,
stated in the study including the involvement of organ dysfunction
that can affect drug metabolism or an
unnecessary risk of side effects.
37 Shinotsuka et.al, 2013, Perceptions and practices regarding delirium, 39 Articles Oversedation has been found to be dangerous
Follow up duration is not sedation and analgesia in critically ill and light sedation, and no-sedation procedures
stated in the study patients- A narrative review are correlated with enhanced patient outcomes.
38 Szumita et .al,2007, Sedation and analgesia in the intensive care 24 RCTs Dexmedetomidine can be an effective agent for
Follow up duration is not unit evaluating the role of dexmedetomidin- And 2160 sedation and analgesia in the ICU. However the
stated in the study A systematic review and met analysis patients lack of clinically significant endpoints in the
trials, the concern about adverse cardiovascular
effects and the relatively high acquisition cost
of this medication reduce its use.

of
39 Tonner et.al,2003, Sedation and analgesia in the intensive care 37 Articles Sedation and analgesia are now seen as an
Follow up duration is not unit-A systematic review and met analysis and 4312 important part of intensive care treatment

ro
stated in the study patients instead of being an inconvenient but required
and minor problem.

-p
40 Vincent et .al,2016, Comfort and patient-centred care without 74 Articles Multimodal analgesia intended to reduce opioid
Follow up duration is not excessive sedation- A Systematic Review use. Sedation is secondary to pain relief and
stated in the study where appropriate, should be dependent on
re
agents that can be titrated to a defined target
level that is subject to frequent examination
lP

and adjustment; the routine usage of

benzodiazepines should be reduced.
41 Weinert et.al,2007,1095 Epidemiology of sedation and sedation 274 Patients While in 32 percent and 21 percent of sedation
na

Days adequacy for mechanically ventilated tests, patients were minimally arousable or
patients in a medical and surgical intensive non-arousable, interestingly, an oversedation
care unit- A prospective Cohort Study rate of <3 percent occurred.
ur

42 Woein et.al,2012,60 Analgesia and sedation of mechanically 54 ICUs and Potential factors that can enhance sedation and
Days ventilated patients– A national survey 108 pain control of manually ventilated patients in
Jo

participants Norwegian ICUs are more formal evaluation of

pain and sedation and the use of written
protocols. Strategies to minimize side effects
should be approached
43 Yang HY et.al,2014,240 Sufentanil for analgesia/sedation in patients 11 Hospitals The effectiveness of sufentanil analgesia is
Days in intensive care unit- A multicenter 544 Patients greater relative to fentanyl. Sufentanil has less
randomized controlled trial physiological involvement and lower frequency
of adverse reactions in patients with ICU.
44 Zalieckas et.al,2011, Sedation and analgesia in the ICU – A 39 Articles Usage of sedation algorithms and emphasis on
Follow up duration is not Systematic review and met analysis sedation protocols are necessary to reduce the
stated in the study total dosage and length of sedatives and
analgesics used.

11
 AREAS OF CONTROVERSY REGARDING ICU SEDATION AND ANALGESIA
A variety of patients are now being admitted to the ICU for mechanical ventilation and other
treatment approaches, but they are treated and intervened differently without any standard steps.
It is clear that there is no evidence-based protocol or means of addressing these ICU patients that
has stopped health practitioners from treating their patients stepwise and logically. Due to these
and other conflicting factors patients in the ICU are treated differently irrespective of their
disease and their need.
An RCT done on Perceptions and practices regarding delirium, sedation and analgesia in

of
critically ill patients shows that over sedation has been shown to be dangerous and light sedation,

ro
and no sedation procedures are correlated with improved patient outcomes. In addition, deep
sedation is frequently used to alleviate anxiety and facilitate amnesia in mechanically ventilated

-p
patients. In addition, deep sedation allows healthcare professionals to offer ICU patient
re
treatment. However, unregulated administration of sedatives is sometimes correlated with over-
lP

sedation, which has been shown to increase the period of mechanical ventilations(18).
On the other hand, other literature strongly disagrees against light sedation and advises against
na

implementing light sedation protocols as these results in accidental loss of endotracheal tubes
and other instruments, increased anxiety, etc. Light sedation may enhance the pain and terrifying
ur

memories that survivors of ICU typically remember(19).

Jo

Deep sedation is also used to relieve anxiety and facilitate amnesia in mechanically ventilated
patients. In addition, deep sedation allows healthcare professionals to offer ICU patient treatment
(18, 20).
Another big controversy and evidence-based practice here in our hospital is the use of
benzodiazepines, but according to study guidelines, sedation methods using non-benzodiazepine
should be favored over sedation with benzodiazepines to increase clinical results in ICU patients.
However, the current literature reports modest differences in outcomes with benzodiazepine
based versus non benzodiazepine-based sedation(3).

12
 DISSCUSSIONS
A systematic review and meta-analysis of 13 RCTs showed that ICU sedation with volatile
anesthetic agents relative to traditional intravenous sedatives, such as propofol or midazolam,
shortened the duration of awakening and extubation. Despite these reductions in waking and
extubation times with unpredictable sedation, no reductions in duration of stay in the ICU or
hospital were noted. Compared to IV sedation, unpredictable sedation administered in the ICU
shortened waking and extubation times(5).
Sedation protocols versus daily disruption of sedation, systematic study and meta-analysis
Dedicates that sedation protocols and daily sedation interruption tend to be similar to techniques

of
targeting lighter sedation levels, although it should be noted that the sedation target should be the

ro
primary objective of management in most patients under mechanical ventilation(21, 22).
Other systematic reviews and meta-analysis indicate that there are no variations between

-p
sedation protocols targeting light sedation levels and daily sedation interruption strategies for
re
mortality, duration of mechanical ventilation and duration of ICU stay. With the use of sedation
lP

procedures targeting lighter sedation levels, the number of days of free mechanical ventilation
was higher and the hospital stay was shorter(23, 24).
na

Randomized controlled trial done by Department of Critical Care, Peking University People's
Hospital, Beijing, China clearly states that insufficient analgesia results in worsening stress,
ur

sleep deprivation, cognitive dysfunction, Anxiety and even delirium(25, 26).Patients who
Jo

received benzodiazepines have a relatively greater risk of delirium; analgesics can reduce the
amount of sedatives required and can further reduce the occurrence of delirium And improve the
prognosis(27).
Clonidine is a feasible alternative to midazolam without significant safety concerns. While both
medications may cause withdrawal symptoms, patients who have been sedated with midazolam
may need additional care for withdrawal after treatment(28).
A trial-based economic assessment shows that clonidine is likely to be a cost-effective sedative
agent relative to midazolam. Neither drug in combination with traditional morphine will provide
ideal sedation. Additional sedation, either with more than one medication or with another agent,
is required to be sustained consistently at the targeted sedation stage. Maintaining individuals
within tight confines of ideal sedation requires frequent evaluation and the ability to provide
rapid rescue sedation(29).

13
REGARDING SEDATION SCALES IN THE ICU
The majority of mechanically ventilated patients need sedation. Preventing unnecessary deep
sedation is a priority in Intensive Care Units (ICUs), associated with adverse effects such as
longer ICU stays, more ICU infections and higher mortality. Lighter sedation can improve these
results, but anxiety can also endanger protection and increase the workload and tension of
workers. Lighter sedation often theoretically exposes patients to pain and distress reported by
ICU survivors (20, 30).

Optimum sedation is unique to the patient, but the prevention of deep sedation should be
considered when maintaining appropriate control of pain and agitation. The most successful
system-level methods for maximizing all aspects of sedation within ICUs are unclear and
introducing and maintaining changes in ICU sedation quality are difficult (31, 32).

of
A standardized tool for evaluating sedation and agitation is required to track sedation levels. It

ro
helps to titrate sedatives and to determine agitated behavior, even though all sedation scales have
their own limits, the 2013 clinical guideline for pain, agitation and delirium in adult ICU patients

-p
has shown that the Richmond agitation sedation scale (RASS) and (SAS) are the most accurate
re
and effective sedation evaluation scales for sedation depth and consistency measurement(16).
lP

In a study comparing the validity and reliability of RASS with the SAS scale, the final result
showed that RASS is reasonable, easy to remember and simple to administer, and that RASS
also has high validity and reliability in surgical and medical patients, in ventilated and non-
na

ventilated patients for sedated and non-sedated adult ICU patients. It also defined that RASS had
advantages in reducing the dose of sedative medication and the duration of mechanical
ur

ventilation(17).
Jo

Evidence is increasing that volatile anesthetic agents are associated with faster extubation times,
better cardiovascular stability with no end-organ toxicity relative to our normal intravenous
agents for short-term critical care sedation. The use of volatile agents in the ICU is a novel
strategy that uses a specialized distribution and scavenging method that needs personnel training
and cultural acceptance. Compared to IV sedation, ICU short-term volatile sedation is
administered by ACD in the ICU shortened awakening and extubation times(33,34). Considering
the difference in serum troponin levels between both arms, volatile anesthetics might have
myocardial protective effect after cardiac surgery even at a sub anesthetic dose(5).

Sedatives are given to 85 percent of patients in the Intensive Care Unit (ICU). The sedatives
most widely used are intravenous benzodiazepines and propofol. These agents are associated
with over-sedation in 40 to 60 percent of patients, which may lead to prolonged intubation,
delirium and drug-induced hypotension(18).

14
 REGARDING PAIN ASSESSMENT AND ANALGESIA IN THE ICU

Pain is one of the causes of anxiety for critically ill patients and can be a positive indication or
warning for some of the pathophysiological issues that need to be corrected, but also a bad cause
of unnecessary stressors for certain pathophysiological problems, but it is difficult to quantify
pain in the ICU, particularly for those who are not aware or unable to talk(35). So several tools
for measuring the pain of critically ill patients has been already developed and validated. A
prospective observational study showed that for uncommunicating patients the commonly and
best pain assessment tools used are BPS (Behavior Pain Scale) and CPOT (Critically-ill Pain
Observation Tool)(3).

of
BPS use three parameters that are facial expression, upper extremity movement, and the

ro
compliance with ventilator, while CPOT use four parameters that are facial expression, muscular

-p
tone (passive movement), upper extremity movement (active), and the compliance with the
re
ventilator. Study indicates that CPOT and BPS showed a strong criterion and distinguish validity
(p < 0.0001). BPS was found to be more specific (91.7 %) than CPOT (70.8 %), but less sensitive
lP

(BPS 62.7 %, CPOT 76.5 %). COPT and BPS scores were significantly correlated with VAS
na

(p < 0.0001). The combination of BPS and CPOT resulted in better sensitivity 80.4 % For
conscious patients who can self-report VAS is the gold standard for evaluation of pain and
ur

VAS≥3 is used to determine patient with pain (11).

Jo

Choice of powerful sedatives and analgesic medications is clearly of importance to our patients’
clinical outcomes(36). In addition to deciding how to dose and titrate, and when we chose to
discontinue these drugs, it is of utmost importance. Increased attention has recently been paid to
adequate titration of sedative and analgesic drugs in critically ill patients, in particular those
treated with mechanical ventilation(37). Patient comfort should be a primary goal in the intensive
care unit (ICU), including adequate pain control, anxiolysis, and prevention and treatment of
delirium. However, adequate balance of sedation and analgesia is difficult. Without rational and
accepted target levels of sedation, it is possible that various health team members may have
disparate treatment priorities, increase the risk of iatrogenic complications and possibly delay
recovery(3).

15
With regard to sedation in the ICU, it is important to note that the treatment of mechanically
ventilated patients under the heading of sedation must first understand the need for adequate
regulation of pain. Pain is a condition mostly encountered by critically ill patients(38). Pain can
be experienced as a consequence of intubation and mechanical ventilation itself, or it can be a
consequence of other routine clinical care such as moving a patient in bed or adjusting tubes and
lines. Pain can be substantial and initiate elements of the stress response. Pain should also be
treated in order to ensure patient satisfaction and potentially reduce accompanying adverse
events. It is possible that patients with adequate pain control may require few or no sedatives, as
noted in the Danish study, although the importance of attention to pain is undeniable, it is equally

of
important to recognize that not all mechanically ventilated patients in the ICU are actually
experiencing pain (6, 11, 39).

ro
-p
Patients at high risk of dying and pain are interviewed for up to 2 weeks after their ICU
experience. This research is significant because it indicates that while universal consideration of
re
the likelihood of pain is required, there is no need for a universal analgesic administration
lP

strategy (40-42). The best way to approach analgesia in mechanically ventilated patients in the
ICU is to interact directly with the patient (2).
na
ur
Jo

16
CONCLUSION
Analgesia and sedation are important therapies in the ICU (11, 30). ICU patients have a delirium
rate of up to 80 per cent, in addition to increased mortality, longer hospital stays, higher hospital
costs and poor long-term outcomes(3).
Sedation protocols and daily sedation interruption do not appear to differ in regard to the
majority of analyzed outcomes (43, 44). The only differences observed were small and had a
high degree of heterogeneity (17, 20). The key indications for the use of these sedatives and
analgesics include: To reduce patient discomfort, to avoid anxiety and agitation, to cause
amnesia, to promote mechanical ventilation, to prevent accidental displacement of endotracheal

of
tubes, and to reduce cell metabolism and so on (15).
Pain should be evaluated and handled appropriately for patients in ICU(40). The final goal of

ro
sedation is to have an awake and alert patient who could perform weaning trials according to
each respected ICU protocols(19).
-p
re
lP
na
ur
Jo

17
RECOMENDATIONS
For pain assessment and analgesia, it is recommended that a combination of BPS be used; it is
recommended that light sedation with daily interruption of sedative infusion or titration of
sedative dose be required for the final purpose of awakening and alertness of a patient who can
conduct a weaning test if there is no contraindication. It is also strongly advised that the use of
RASS is an important sedation assessment tool in adult ICU patients and the implementation of a
revised ICU analgesia, sedation and delirium protocol has been associated with enhanced RASS
and RSS assessment and documentation; reduced hourly benzodiazepine dose; and decreased
delirium and median durations of mechanical ventilation, ICU stay, and hospitalization. (9).

of
As regards the pharmacological option of sedatives, Propofol is strongly recommended for short-

ro
term sedation and is superior to midazolam and other sedatives. It is just as effective for medium
and long-term sedation as midazolam for more than 72 hours. So we can use Propofol for both

-p
short-term and long-term sedation methods safely(45). It is again recommended that the use of
re
ketamine as an alternative sedative agent in adult ICU patients is very necessary, particularly in
lP

patients with asthma and hypotensive blood pressure and CPOT in critically ill, mechanically
ventilated adult ICU patients. And for a conscious adult ICU patient, it is advised to use VAS for
na

validated pain assessment (18,20).

ur

LIMITATIONS AND CHALLENGE

Jo

This review article had its limitation and challenges. The authors thought that the limitations are
acceptable and challenges are over come accordingly. Luck of very recent studies and using of
different article types was one limitation and challenges which has been overcome by taking
studies done in the past 20 years and considering recommendation.

Availability of a variety of sedation and pain assessment tools and differences in utilization of
these tools set up to set up was another limitation and challenge and we have overcome it by just
taking the most widely used tools and by localizing the guideline to a resource limited localized
set up .

18
SUMMARY OF SEDATION AND PAIN ASSESSMENT TOOLS
In this systematic review and evidence based guideline different sedation assessment tools have
been used, of which the Blooms Burry Sedation scale is the one. In the Blooms Burry Sedation
patients having sedation scores -3 up to 2 do not need any sedative, while those who have 3 and
above are in need of sedatives accordingly (Table 3).

Table 3: BLOOMS BURRY SEDATION SCALE (BBSS)

SEESDATION SCORS BEHAVIOR OF THE PATIENT

3 Agitated and restless

of
2

ro
Awake and comfortable

-p
1
Aware but calm
re
0
Roused by voice
lP

-1
Roused by touch
na

-2
Roused by painful stimuli
ur

-3
Unrousable
Jo

A Natural sleep
P

Paralysed

19
For critically ill patients we can use behavioural pain Scales. The tool principally considers
Facial expression, Limbic movement and Complains with a mechanical ventilators (Table 4).

Table 4: BHAVIORAL PAIN SCALE (BPS)

ITEMs DESCRIPTION SCOREs

Relaxed 1

FACIAL EXPRESSION Partially tightened...(Brow lowering) 2

of
Fully tightened.....(Eyelid closing) 3

ro
Grimacing 4

-p 1
re
No movement
2
lP

UPPER LIMBS
Partially bent
na

3
Fully bent with finger flexion
ur

4
Permanently retracted
Jo

Tolerating Movement 1

COMPLIANS 2
WITH VENTILATION Coughing but tolerating ventilation most of
the time
3
Fighting ventilator
4
Unable to control ventilation

20
The sedation-Agitation Scale a very important tool to assess both levels of sedation and
agitation. In this tool scores 1-2 are for unawake patients and doesn’t request use of sedative,
while 3-7 are awake patients of which 5-7 are in need of Sedative use (Table 5).

Table 5: Sedation-Agitation Scale (SAS)

SCORE DESRPTION STATE

7 Dangerous agitation
A
6 Very agitated W
A
5 K

of
Agitated E
4

ro
Calm and Cooperative
3
Sedated
-p
re
2 Very Sedated N
lP

O
T
A
na

1 W
Unarousable A
ur

K
E
Jo

21
The Richmond Agitation Sedation Scale the most important tool that is frequently used. Patients
who have score of 1-4 are in state of restless to combative and needs sedation. Those having
scores -5 – 0 are in state of unarousable to alert and calm so that do not need sedation (Table 6).

Table 6: Richmond Agitation Sedation Scale (RASS)

SCORE TERMS DESCRIPTION

+4 Combative Overtly combative or violent; immediate danger to staff

+3 Very agitated Pulls on or removes tube(s) or catheter(s) or has aggressive behaviour

towards staff
Agitated Frequent nonpurposeful movement or patient–ventilator dyssynchrony

of
+2
+1 Restless Anxious or apprehensive but movements not aggressive or vigorous

ro
0 Alert& calm

-p
Considered Normal and obeys commands
-1 Drowsy Not fully alert, but has sustained (more than 10 s) awakening, with eye
re
contact in response to voice
-2 Light sedation Briefly (less than 10 s) awakens with eye contact in response to voice
lP

-3 Moderate sedation Any movement (but no eye contact) in response to voice

-4 Deep sedation No response to voice, but any movement in response to physical

na

stimulation
-5 Unarousable No response to voice or physical stimulation
ur
Jo

22
 For the assessment of pain in critically ill patients we preferentially use the Critically Ill Pain
Observation Tool. This tool considers facial expression, body movement, muscle tension,
copmlaince with mechanical ventilators and vocalization for extubated patients (Table 7).

Table 7: CRITICALLY ILL PAIN OBSERVATION TOOL (CPOT)

INDICATORs DESCRIPTIONs SCOREs

FACIAL EXPRESSION RELAXED,NUETRAL 0

TENSE 1

GRIMACING 2

of
BODY MOVEMENT ABSENCE OF MOVEMENTs 0

ro
PROTECTION 1

-p
re
RESTLESSNESS 2
lP

MUSCLE TENSION RELAEDX 0

na

TENSE OR RIGID 1
ur

VERY TENSE/RIGID 2
Jo

COMLIANS WITH TOLARATING VENTILATOR 0

VENITLATOR
(INTUBAED PTs)
COUGHING,BUT TOLERATEs 1

FIGHTING VENTILATOR 2

VOCALIZATION TALKING IN NORMAL TONE 0

(EXTUBATED PTs)
SIGHING,MAONING 1
CRYING OUT,SOBBING 2

Finally flow diagram was drawn based the collected information’s from the literatures. The flaw
is made after it has been contextualized into limited setups (Fig 2) .

23
 Assess sedation scale using RASS
score

DROWSY/SEDATED CALM/ ALERT

AGITATED/RESTLESS
RASS <0 RASS = 0
RASS >0

of
RASS -4 to -5 RASS -1 to -3 ASSESS PAIN
USING VAS

ro
NEEDS AIRWAY PROTECTION: FOLLOW AND
-p
IF VAS ≥3 GIVE: IF VAS < 3
re
=>INTUBABATE USING
CONTINUE FENTANYL(25-50mcg/hr)
DIAZEPAM (5-10mg), PROPOFOL
(1.5-2.5mg/kg, FENTANYL (50-
USUAL ICU CONTINUE
lP

100mcg), TRAMADOL (50-100mg) MORPHINE(2-5mg/hr)

CARE USUAL CARE
TRAMADOL (50-100mg/8hr)
na

ASSESS PAIN USING: BPS

ur

ASSESS PAIN
infusion at
Jo

USING BPS
BPS >5 OR CPOT ≥ 3

TREAT PAIN WITHIN

30MIUTES
BPS<5 or
FENTANYL: 25-50µg/kg/hr
CPOT<3 BPS<5 or CPOT<3
MORPHINE: 2-4mg/hr BPS ≥5 OR CPOT ≥3
CONTINUE SEDATION WITH:
TTRAMADOL: 50-100mg/8hrs USUAL CARE GIVE: PROPOFOL PROPOFOL 6-
AND FENTANYL 12mg/kg/hr
care
If for >72hrs titrate doses
10-50%) KETAMINE
20-50mg boles and
1-5mcg/kg respectively 10-50µg/kg/hr for
hypotensive patients.

24
Figer 2: PRACTICE GUIDELINE ON ADULT SEDATION AND ANALGESIA FOR A RESOURCE LIMITED ICU SETTINGS

ABBREVIATINS AND ACRONYM

ASA American society of anaesthesiologists

BPS Behavioral pain scale

CPOT Critical care pain observation tool

of
GURH Gondar university referral hospital

ro
ICU Intensive care unit

RASS -p
Richmond agitation sedation scale
re
lP

RCT Randomized controlled trail

RSS Ramsay sedation scale

na

SAS Sedation agitation scale

ur

VAS Visual analogue score

Jo

25
DECLARATION

The authors declares that this is an original work of the authors

Ethical approval

Not required
CONSENT FOR PUBLICATION
Not applicable for this publication

COMPETING OF INTERSET

of
All the authors declared that there is no competing of interest

ro
FUNDING

-p
None re
lP
na

Provenance and peer review

Not commissioned externally peer reviewed.
ur
Jo

26
REFFERNCES

1.Zalieckas J, Weldon C, editors. Sedation and analgesia in the ICU. Seminars in pediatric
surgery; 2015: Elsevier.
2.Keogh SJ, Long DA, Horn DV. Practice guidelines for sedation and analgesia management of
critically ill children: a pilot study evaluating guideline impact and feasibility in the PICU. BMJ
Open. 2015;5(3):e006428-e.
3.Kress JP, Pohlman AS, Hall JB. Sedation and analgesia in the intensive care unit. American
journal of respiratory and critical care medicine. 2002;166(8):1024-8.
4.Lavrentieva A, Depetris N, Rodini I. Analgesia, sedation and arousal status in burn patients:
the gap between recommendations and current practices. Annals of Burns and Fire Disasters.
2017;30(2):135.
5.Fraser GL, Devlin JW, Worby CP, Alhazzani W, Barr J, Dasta JF, et al. Benzodiazepine versus

of
nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic
review and meta-analysis of randomized trials. Read Online: Critical Care Medicine| Society of

ro
Critical Care Medicine. 2013;41(9):S30-S8.
6.Tonner PH, Weiler N, Paris A, Scholz J. Sedation and analgesia in the intensive care unit.

-p
Current Opinion in Anesthesiology. 2003;16(2):113-21.
7.Kim HY, Lee JE, Kim HY, Kim J. Volatile sedation in the intensive care unit: A systematic
re
review and meta-analysis. Medicine. 2017;96(49).
8.Weinert CR, Calvin AD. Epidemiology of sedation and sedation adequacy for mechanically
lP

ventilated patients in a medical and surgical intensive care unit. Critical care medicine.
2007;35(2):393-401.
9.Wøien H, Stubhaug A, Bjørk I. Analgesia and sedation of mechanically ventilated patients–a
na

national survey of clinical practice. Acta Anaesthesiologica Scandinavica. 2012;56(1):23-9.

10.Fraser GL, Riker RR. Sedation and analgesia in the critically ill adult. Current Opinion in
ur

Anesthesiology. 2007;20(2):119-23.
11.Vincent J-L, Shehabi Y, Walsh TS, Pandharipande PP, Ball JA, Spronk P, et al. Comfort and
Jo

patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med.
2016;42(6):962-71.
12.Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, et al. Monitoring
sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-
Sedation Scale (RASS). Jama. 2003;289(22):2983-91.
13.Mukhopadhyay A, Tai BC, Remani D, Phua J, Cove ME, Kowitlawakul Y. Age related
inverse dose relation of sedatives and analgesics in the intensive care unit. PLoS One.
2017;12(9):e0185212.
14.Devabhakthuni S, Armahizer MJ, Dasta JF, Kane-Gill SL. Analgosedation: a paradigm shift
in intensive care unit sedation practice. Annals of Pharmacotherapy. 2012;46(4):530-40.
15.Devlin JW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the
ICU: benzodiazepines, propofol, and opioids. Critical care clinics. 2009;25(3):431-49.
16.Reade MC, Finfer S. Sedation and delirium in the intensive care unit. New England Journal of
Medicine. 2014;370(5):444-54.
17.Rowe K, Fletcher S. Sedation in the intensive care unit. 2008;8(2):50-5.
18.Shinotsuka CR, Salluh JIF. Perceptions and practices regarding delirium, sedation and
analgesia in critically ill patients: a narrative review. Revista Brasileira de Terapia Intensiva.
2013;25(2):155.

27
19.Baron R, Binder A, Biniek R, Braune S, Buerkle H, Dall P, et al. Evidence and consensus
based guideline for the management of delirium, analgesia, and sedation in intensive care
medicine. Revision 2015 (DAS-Guideline 2015)–short version. GMS German Medical Science.
2015;13.
20.Schweickert WD, Kress JP. Strategies to optimize analgesia and sedation. Crit Care. 2008;12
Suppl 3(Suppl 3):S6-S.
21.MacLaren R, Plamondon JM, Ramsay KB, Rocker GM, Patrick WD, Hall RI. A prospective
evaluation of empiric versus protocol‐based sedation and analgesia. Pharmacotherapy: The
Journal of Human Pharmacology and Drug Therapy. 2000;20(6):662-72.
22.Martin J, Franck M, Fischer M, Spies C. Sedation and analgesia in German intensive care
units: how is it done in reality? Results of a patient-based survey of analgesia and sedation.
Intensive Care Med. 2006;32(8):1137-42.
23.Brush DR, Kress JP. Sedation and analgesia for the mechanically ventilated patient. Clinics in
chest medicine. 2009;30(1):131-41.

of
24.Burry L, Rose L, McCullagh IJ, Fergusson DA, Ferguson ND, Mehta S. Daily sedation
interruption versus no daily sedation interruption for critically ill adult patients requiring invasive

ro
mechanical ventilation. Cochrane Database of Systematic Reviews. 2014(7).
25.Martin J, Parsch A, Franck M, Wernecke KD, Fischer M, Spies C. Practice of sedation and

-p
analgesia in German intensive care units: results of a national survey. Critical Care.
2005;9(2):R117.
re
26.Meiser A, Laubenthal H. Inhalational anaesthetics in the ICU: theory and practice of
inhalational sedation in the ICU, economics, risk-benefit. Best Practice & Research Clinical
lP

Anaesthesiology. 2005;19(3):523-38.
27.Hutton B, Burry LD, Kanji S, Mehta S, Guenette M, Martin CM, et al. Comparison of
na

sedation strategies for critically ill patients: a protocol for a systematic review incorporating
network meta-analyses. Systematic reviews. 2016;5(1):1-7.
28.Park G, Coursin D, Ely EW, England M, Fraser GL, Mantz J, et al. Commentary. Balancing
ur

sedation and analgesia in the critically ill. Critical care clinics. 2001;17(4):1015-27.
29.Yang H, Sun R, Chang Y, Fu Y, Li B, Qin B, et al. A multicenter randomized controlled trial
Jo

of sufentanil for analgesia/sedation in patients in intensive care unit. Zhonghua wei zhong bing ji
jiu yi xue. 2014;26(2):94-100.
30.Owen GD, Stollings JL, Rakhit S, Wang L, Yu C, Hosay MA, et al. International Analgesia,
Sedation, and Delirium Practices: a prospective cohort study. J Intensive Care. 2019;7:25-.
31.Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines
for the management of pain, agitation, and delirium in adult patients in the intensive care unit.
Critical care medicine. 2013;41(1):263-306.
32.Jerath A, Ferguson ND, Steel A, Wijeysundera D, Macdonald J, Wasowicz M. The use of
volatile anesthetic agents for long-term critical care sedation (VALTS): study protocol for a pilot
randomized controlled trial. Trials. 2015;16(1):560.
33.Patanwala AE, Martin JR, Erstad BL. Ketamine for analgosedation in the intensive care unit:
a systematic review. Journal of Intensive Care Medicine. 2017;32(6):387-95.
34.Pradelli L, Povero M, Bürkle H, Kampmeier T-G, Della-Rocca G, Feuersenger A, et al.
Propofol or benzodiazepines for short-and long-term sedation in intensive care units? An
economic evaluation based on meta-analytic results. ClinicoEconomics and Outcomes Research:
CEOR. 2017;9:685.

28
35.Dale CR, Kannas DA, Fan VS, Daniel SL, Deem S, Yanez ND, 3rd, et al. Improved
analgesia, sedation, and delirium protocol associated with decreased duration of delirium and
mechanical ventilation. Ann Am Thorac Soc. 2014;11(3):367-74.
36.Szumita PM, Baroletti SA, Anger KE, Wechsler ME. Sedation and analgesia in the intensive
care unit: evaluating the role of dexmedetomidine. American journal of health-system pharmacy.
2007;64(1) 37.Ahlers SJ, van Gulik L, van der Veen AM, van Dongen HP, Bruins P, Belitser
SV, et al. Comparison of different pain scoring systems in critically ill patients in a general ICU.
Critical care. 2008;12(1):R15.
38.Deffland M, Spies C, Weiss B, Keller N, Jenny M, Kruppa J, et al. Effects of pain, sedation
and delirium monitoring on clinical and economic outcome: A retrospective study. PLoS One.
2020;15(9):e0234801-e.
Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci. 2015;13:Doc19-Doc.
39.Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early
physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised

of
controlled trial. The Lancet. 2009;373(9678):1874-82.
40.Sessler CN, Pedram S. Protocolized and target-based sedation and analgesia in the ICU.

ro
Anesthesiology Clinics. 2011;29(4):625-50.
41.Sessler CN, Varney K. Patient-focused sedation and analgesia in the ICU. Chest.
2008;133(2):552-65.
-p
42.Patel RP, Gambrell M, Speroff T, Scott TA, Pun BT, Okahashi J, et al. Delirium and sedation
re
in the intensive care unit (ICU): survey of behaviors and attitudes of 1,384 healthcare
professionals. Critical care medicine. 2009;37(3):825.
lP

43.Payen J-F, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou J-L, et al. Current practices
in sedation and analgesia for mechanically ventilated critically ill patients: a prospective
na

multicenter patient-based study. The Journal of the American Society of Anesthesiologists.

2007;106(4):687-95.
44.Rozendaal FW, Spronk PE, Snellen FF, Schoen A, van Zanten AR, Foudraine NA, et al.
ur

Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay

compared to a conventional regimen: a centre randomised, cross-over, open-label study in the
Jo

Netherlands. Intensive Care Med. 2009;35(2):291-8.

29
Highlights
 Critically ill patients shall be awake, alert without pain, anxiety and delirium.
 Analgesia and sedation in the ICU shall be given as per needed after determined they
are in need of.
 Sedation breaks are paramount important as equal as spontaneous breathing trials.
 Unnecessary deep sedations will increase hospital and personnel costs by increasing
length of ICU stay .

of
ro
-p
re
lP
na
ur
Jo