2020 International Consensus on First Aid Science With Treatment Recommendations
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Circulation
2020 International Consensus on First Aid
Science With Treatment Recommendations
ABSTRACT: This is the summary publication of the International Eunice M. Singletary, MD,
Liaison Committee on Resuscitation’s 2020 International Consensus Chair
on First Aid Science With Treatment Recommendations. It addresses David A. Zideman, LVO,
the most recent published evidence reviewed by the First Aid Task QHP(C), MBBS, Vice
Force science experts. This summary addresses the topics of first aid Chair
methods of glucose administration for hypoglycemia; techniques for Jason C. Bendall, MBBS,
cooling of exertional hyperthermia and heatstroke; recognition of MM, PhD
acute stroke; the use of supplementary oxygen in acute stroke; early David C. Berry, PhD, MHA
Vere Borra, PhD
or first aid use of aspirin for chest pain; control of life-threatening
Jestin N. Carlson, MD, MS
bleeding through the use of tourniquets, hemostatic dressings, direct
Pascal Cassan, MD
pressure, or pressure devices; the use of a compression wrap for Wei-Tien Chang, MD, PhD
closed extremity joint injuries; and temporary storage of an avulsed Nathan P. Charlton, MD
Downloaded from http://ahajournals.org by on October 28, 2020
tooth. Additional summaries of scoping reviews are presented for Therese Djärv, MD, PhD
the use of a recovery position, recognition of a concussion, and 6 Matthew J. Douma, MSN,
other first aid topics. The First Aid Task Force has assessed, discussed, RN
and debated the certainty of evidence on the basis of Grading of Jonathan L. Epstein,
Recommendations, Assessment, Development, and Evaluation criteria MEMS, NRP
and present their consensus treatment recommendations with Natalie A. Hood, MD,
evidence-to-decision highlights and identified priority knowledge gaps MBBS
for future research. David S. Markenson, MD,
MBA
Daniel Meyran, MD
Aaron M. Orkin, MD, MSc,
MPH, PhD(c)
Tetsuya Sakamoto, MD,
PhD
Janel M. Swain, BSc, BEd,
ACP
Jeff A. Woodin, NRP
On behalf of the First Aid
Science Collaborators
Key Words: AHA Scientific
Statements ◼ first aid ◼ medical
emergencies ◼ trauma
© 2020 American Heart Association,
Inc., European Resuscitation Council,
and International Liaison Committee on
Resuscitation
https://www.ahajournals.org/journal/circ
S284 October 20, 2020 Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897Singletary et al First Aid: 2020 CoSTR
CONTENTS Manual Cervical Spine Stabilization (FA
1547: ScopRev) …………………………..….S316
Evidence Evaluation Process and Types of
Cervical Spinal Motion Restriction
Reviews……………………………………...............S285
(FA 772: ScopRev) ……………….......…..….S317
Definition of First Aid…………………………….….S286
First Aid Dressings for Superficial Thermal
Selection of Topics…………………………………..S287
Burns (FA New 2019: ScopRev) ………....….S318
Selection of Type of Review………………………...S287
Compression Wrap for Closed Extremity
Topics Reviewed in 2020……………………………S287 Joint Injuries (FA 511: SysRev) ………...…….S319
First Aid for Medical Emergencies………………….S287 Storage of an Avulsed Permanent Tooth
Methods of Glucose Administration for Before Replantation (FA 794: SysRev) ….......S321
Mild Hypoglycemia (FA 1585: SysRev) .……..S288 Topics Not Reviewed in 2020….............................S325
Dietary Sugars for Treatment of Acknowledgments….............................................S325
Hypoglycemia (FA 795: EvUp) ………...…….S290 Disclosures….........................................................S326
Cooling of Heatstroke and Exertional References........................................................….S327
Hyperthermia (FA 1548: SysRev) ……...…….S291
Recognition of Anaphylaxis by First Aid
T
Providers (FA 513: ScopRev) ………......…....S295 he 2020 International Consensus on Cardio-
Second Dose of Epinephrine for pulmonary Resuscitation (CPR) and Emergency
Anaphylaxis (FA 500: ScopRev) ……………..S295 Cardiovascular Care (ECC) Science With Treat-
First Aid Stroke Recognition (FA 801: ment Recommendations (CoSTR) is the fourth in a
SysRev) ……………....................………..….S296 series of annual summary publications from the Interna-
First Aid Supplementary Oxygen for Acute tional Liaison Committee on Resuscitation (ILCOR). This
Stroke (FA 1549: SysRev) ………...………….S300 2020 CoSTR for first aid includes new topics addressed
First Aid Administration of Aspirin for by systematic reviews performed within the past 12
Chest Pain: Early Compared With Late months. It also includes updates of the first aid treat-
(FA 586: SysRev) …………...………………...S303 ment recommendations published from 2010 through
First Aid Interventions for Presyncope 2019 that are based on additional evidence evaluations
(2019 CoSTR, FA 798: SysRev) …….…….….S305 and updates. As a result, this 2020 CoSTR for first aid
Optimal Position for Shock (FA 520: represents the most comprehensive update since 2010.
Downloaded from http://ahajournals.org by on October 28, 2020
EvUp) ………………...............……………...S305
Recovery Position for Persons With
Decreased Level of Consciousness of EVIDENCE EVALUATION PROCESS AND
Nontraumatic Etiology Not Requiring TYPES OF REVIEWS
Rescue Breathing or Chest Compressions The 3 major types of evidence evaluation supporting
(FA 517: ScopRev) ………...............………...S306 this 2020 publication are the systematic review (SysRev),
First Aid for Trauma Emergencies…………….…....S307 the scoping review (ScopRev), and the evidence update
Control of Severe, Life-Threatening (EvUp). The SysRev is a rigorous process following strict
External Bleeding: Pressure Dressings, methodology to answer a specific question. Each SysRev
Bandages, Devices, or Proximal Manual ultimately resulted in the generation of the task force
Pressure (FA: New 2019 SysRev) …...............S307 CoSTR included in this publication. The SysRevs were
Control of Severe, Life-Threatening External performed by a knowledge synthesis unit, an expert
Extremity Bleeding: Tourniquets (FA 768, systematic reviewer, or by the First Aid Task Force, and
1543, 1549: SysRev)…….....................……..S309 many have resulted in separately published SysRevs.
Control of Severe, Life-Threatening External To begin the SysRev, the question to be answered
Bleeding: Hemostatic Dressings (FA 769: was phrased in terms of the population, interven-
SysRev) …………….........………………..….S312 tion, comparator, outcome, study design, time frame
Control of Severe, Life-Threatening External (PICOST) format. The methodology used to identify the
Bleeding: Hemostatic Devices (2020 New FA: evidence was based on the Preferred Reporting Items for
SysRev) …………………………………….….S314 Systematic Reviews and Meta-Analyses.1 The approach
Pediatric Tourniquet Designs for Life- used to evaluate the evidence was based on that pro-
Threatening Extremity Hemorrhage posed by the Grading of Recommendations, Assess-
(FA New 2019: ScopRev) ……….………..….S315 ment, Development, and Evaluation (GRADE) working
Simple Single-Stage Concussion Scoring group.2 The outcomes to be searched were determined
System(s) in the First Aid Setting (FA 799: through discussion with the task force and the system-
ScopRev) ................................................….S316 atic reviewer, and consensus was reached to rank each as
Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897 October 20, 2020 S285Singletary et al First Aid: 2020 CoSTR
critical, important, or less important. Using this approach The third type of evidence evaluation supporting this
for each of the predefined outcomes, the task force 2020 CoSTR for first aid is an EvUp. EvUps are generally
rated as high, moderate, low, or very low the certainty/ performed to identify new studies published after the
confidence in the estimates of effect of an intervention most recent First Aid Task Force evidence evaluation,
or assessment across a body of evidence. Randomized typically through the use of search terms and method-
controlled trials (RCTs) generally began the analysis as ologies from previous reviews. These EvUps were per-
high-certainty evidence, and observational studies gen- formed by task force members, collaborating experts,
erally began the analysis as low-certainty evidence; ex- or members of Council writing groups. The EvUps are
amination of the evidence using the GRADE approach cited in the body of this publication with a note as to
could result in downgrading or upgrading the certain- whether the task force agreed that the identified evi-
ty of evidence. For additional information, refer to the dence suggested the need to consider a new SysRev. All
CoSTR section titled Evidence Evaluation Process and EvUps are reproduced in their entirety in Appendix C in
Management of Potential Conflicts of Interest.3,3a Disclo- the Supplemental Materials.
sure information for writing group members is listed in In this publication, no change in treatment recom-
Appendix 1. Disclosure information for peer reviewers is mendations resulted from a ScopRev or an EvUp; if
listed in Appendix 2. substantial new evidence was identified, the task force
Draft 2020 first aid CoSTRs were posted on the recommended consideration of a SysRev.
ILCOR website4 for public comment between October
19, 2018, and January 5, 2019, with comments
accepted through January 19, 2019. The 12 first DEFINITION OF FIRST AID
aid draft CoSTR statements were viewed a total of The evidence evaluation process for the First Aid Task
39 011 times, and readers provided 21 comments. All Force began with a review of the working definition of
comments were discussed by the task force and first aid, including goals and key principles as viewed by
resulted in elimination of a minor wording discrepancy task force members from the international perspective.
between the treatment recommendation in one draft First aid is the initial care provided for an acute ill-
CoSTR and the evidence-to-decision table. ness or injury. The goals of first aid include preserving
This summary statement contains the final wording life, alleviating suffering, preventing further illness or
of the CoSTR statements as approved by the ILCOR task injury, and promoting recovery. First aid can be initiated
Downloaded from http://ahajournals.org by on October 28, 2020
forces and by the ILCOR member councils after review by anyone in any situation, including self-care. General
and consideration of the evidence as well as the com- characteristics of the provision of first aid, at any level
ments posted online in response to the draft CoSTRs. of training include the following:
Within this publication, each topic includes the PICOST • Recognizing, assessing, and prioritizing the need
as well as the CoSTR, an expanded section on justifica- for first aid
tion and evidence-to-decision framework highlights, and • Providing care using appropriate competencies
a list of knowledge gaps suggesting future research stud- and recognizing limitations
ies. An evidence-to-decision table is included for each • Seeking additional care when needed, such as
CoSTR in Appendix A in the Supplemental Materials. activating the emergency medical services system
The second major type of evidence evaluation or other medical assistance
performed to support this 2020 CoSTR for first aid is a Key principles include the following:
ScopRev. ScopRevs are designed to identify the extent, • First aid should be medically sound and based on
range, and nature of evidence on a topic or a question, the best available scientific evidence.
and they were performed by topic experts in consulta- • First aid education should be universal; everyone
tion with the First Aid Task Force. The task force ana- should learn first aid.
lyzed the identified evidence and determined its value • Helping behaviors should be promoted; everyone
and implications for first aid practice or research. The should act.
rationale for the ScopRev, the summary of evidence, The scope of first aid and helping behaviors varies and
and task force insights are all highlighted in the body may be influenced by environmental, resource, training,
of this publication. If the ScopRev did not identify and regulatory factors.
evidence that justified consideration of a SysRev, the Because the scope of first aid is not purely scientific,
most recent treatment recommendations are reiterated. the use of the GRADE evidence-to-decision framework
The task force noted whether the ScopRev identified allowed consideration of literature not typically included
substantive evidence suggesting the need for a future in SysRevs, including studies such as case series or basic
SysRev to support the development of an updated science studies, or consideration of issues related to im-
CoSTR. All ScopRevs are included in their entirety in plementation and feasibility, resources required, health
Appendix B in the Supplemental Materials. equity, and cost, all with an international perspective.
S286 October 20, 2020 Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897Singletary et al First Aid: 2020 CoSTR
For SysRevs and ScopRevs, task force members consid- • Dietary sugars for treatment of hypoglycemia (FA
ered and discussed these aspects with the consensus on 795: EvUp)
science to guide treatment recommendations. • Heatstroke cooling (FA 1548: SysRev)
• Recognition of anaphylaxis by first aid providers
(FA 513: ScopRev)
SELECTION OF TOPICS • Second dose of epinephrine for anaphylaxis (FA
The Chair, Vice Chair, and 15 members of the First Aid 500: ScopRev)
Task Force representing 5 ILCOR member councils met • Stroke recognition (FA 801: SysRev)
in autumn 2017 to review the first aid topics and ques- • Supplementary oxygen in acute stroke (FA 1549:
tions that were evaluated in 2005, 2010, and 2015 SysRev)
as well as past research questions formulated in the • Early/late aspirin for chest pain (FA 586: SysRev)
PICOST style that were never reviewed. The task force • Presyncope (FA 798: SysRev)
reviewed new questions submitted to the task force af- • Optimal position for shock (FA 520: EvUp)
• Recovery position (FA 517: ScopRev)
ter publication of the 2015 first aid CoSTR. Topics were
First Aid for Trauma Emergencies
considered based on any identified new evidence that
• Control of life-threatening bleeding (combined
might affect previous ILCOR treatment recommendation
SysRev):
strength or direction, new topics identified as priorities
– Direct pressure, pressure dressings, pressure
for ILCOR member organizations, and topics with areas
points (FA 530)
of controversy. The wording of all PICOST questions was
– Tourniquet versus direct pressure, tourniquet
deliberated and, in some cases, updated to reflect rec-
design, manufactured versus improvised tourni-
ommended changes in the evidence evaluation process
quets (FA 768, 1543, 1549)
after the 2015 CoSTR. An abbreviated literature search
– Hemostatic dressings versus direct pressure or
was used to determine the volume of new evidence on
tourniquet, types of hemostatic dressings (FA
a topic that might signal a need to rereview a previously 769)
evaluated PICOST question. A ranked scored priority list – Hemostatic devices: junctional tourniquets,
of questions was then created. wound clamp (FA 2019)
• Pediatric tourniquets (FA 768 Peds: ScopRev)
• Concussion recognition (FA 799: ScopRev)
Downloaded from http://ahajournals.org by on October 28, 2020
SELECTION OF TYPE OF REVIEW • Manual cervical spine stabilization (FA 1547: ScopRev)
The general evidence evaluation process for first aid • Cervical spine motion restriction (FA 772: ScopRev)
started with 5 of the top-ranked first aid questions that • Superficial thermal injury dressings (FA 1545:
were related to the control of life-threatening bleed- ScopRev)
ing. These were combined and expanded to form a • Compression wrap (FA 511: SysRev)
complex PICOST, a collection of questions (ie, rather • Dental avulsion (FA 794: SysRev)
than a single question) assigned to a knowledge syn-
thesis unit for a systematic review with assistance from
task force content experts. The size and complexity of FIRST AID FOR MEDICAL
this review led to formation of 4 separate CoSTR top- EMERGENCIES
ics. Three additional PICOST question topics were pri-
Important medical first aid topics for 2020 included meth-
oritized for review by expert systematic reviewers with
ods of glucose administration for hypoglycemia, dietary
assistance from content experts within the First Aid
sugars for treatment of hypoglycemia, cooling for heat-
Task Force. Five topics underwent SysRevs by task force stroke and exertional hyperthermia, recognition of ana-
teams with assistance from approved outside con- phylaxis, second dose of epinephrine for anaphylaxis,
tent experts and reviewers. Eight topics were known stroke recognition, use of supplementary oxygen for acute
to have limited new evidence and were selected for stroke, early and late aspirin administration for chest pain,
ScopRevs. An additional 2 topics underwent EvUps immediate interventions for presyncope, and optimal po-
without a SysRev or a ScopRev. New topics are noted sition for shock and recovery position. The recommenda-
in the list of topics. tions stemming from the review of cooling for heatstroke
are particularly relevant in light of increased risk of both
heatstroke and exertional hyperthermia worldwide.
TOPICS REVIEWED IN 2020 ScopRevs included topics with known limited evi-
First Aid for Medical Emergencies dence such as the recognition of anaphylaxis and cervical
• Methods of glucose administration for hypoglyce- spine motion restriction and manual stabilization. These
mia (FA 1585: SysRev) ScopRevs did not identify new literature to justify new
Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897 October 20, 2020 S287Singletary et al First Aid: 2020 CoSTR
SysRevs or consideration of a change in the corresponding – Resolution of hypoglycemia (important), defined
2015 first aid treatment recommendations. However, the as elevation of the blood glucose concentration
ScopRev on the use of a recovery position was unique in above the authors’ threshold for determining
that the target population of interest was changed from hypoglycemia (dichotomous outcome; yes/no)
“persons who are unresponsive but breathing normally” – Time to resolution of hypoglycemia (important),
to “adults and children with decreased level of conscious- defined as the time from the administration of
ness caused by medical illness that do not meet criteria the sugar containing solution until the blood
for the initiation of rescue breathing or chest compres- glucose concentration rose above the thresh-
sions (CPR).” This change is intended to represent more old for the authors’ definition of hypoglycemia
typical presentations that will be encountered by first aid (continuous outcome)
providers and may require the use of a recovery position. – Any adverse event (important); any event result-
The goal was to identify evidence that was missed when ing from the administration of sugar, as defined
the search was limited to only those who were unrespon- by the study authors (eg, aspiration)
sive and breathing normally. – Administration delay (important), defined as the
delay in administering the sugar as a result of
the administration arm (dichotomous outcome;
Methods of Glucose Administration for yes/no)
Mild Hypoglycemia (FA 1585: SysRev) • Study design: Randomized and nonrandomized
Rationale for Review clinical trials; observational studies were included;
The most recent CoSTR on this topic was published unpublished studies (eg, conference abstracts, trial
in 20155,6 and was developed in conjunction with a protocols, methods papers) were excluded
SysRev, published in 2017,7 of dietary forms of glucose • Time frame: All years and all languages were
compared with glucose tablets to treat symptomatic included provided there was an English abstract to
hypoglycemia. For 2020, the task force prioritized a December 22, 2017, with an update performed on
SysRev, completed in 2019,8 of methods of glucose July 11, 2018.
administration in first aid for suspected hypoglycemia. Studies were included if glucose, table sugar
(sucrose), or liquid sugar (eg, corn syrup) was admin-
Population, Intervention, Comparator, Outcome,
istered by any enteral route appropriate for use by first
Study Design, and Time Frame
Downloaded from http://ahajournals.org by on October 28, 2020
aid providers (buccal [inserted on the mucosa inside the
• Population: Adults and children with sus-
cheek], sublingual [under the tongue], oral [on top of
pected hypoglycemia (out-of-hospital setting)
the tongue]). Glucose and sugar formulations could
(Note: Neonates are excluded because we believe
include spray, gel, liquid, paste, syrup, or tablet form.
the identification of hypoglycemia in this age
Buccal administration was defined as application to the
group requires specialized diagnostic and treat-
cheek mucosa and sublingual administration as applica-
ment processes well beyond first aid.)
tion under the tongue, both without swallowing. Mild
• Intervention: Administration of glucose by any enteral
hypoglycemia was defined as the typical early signs and
route appropriate for use by first aid providers
symptoms of hypoglycemia but with preserved ability
• Comparator: Administration of glucose by another
to swallow and follow commands.
enteral route appropriate for use by first aid
International Prospective Register of Systematic
providers
Reviews (PROSPERO) Registration: CRD42018088637
• Outcome:
– Resolution of symptoms (critical), defined as Consensus on Science
the reversal of the initial symptoms as reported The SysRev identified 4 studies enrolling a total of 83
by the person with suspected hypoglycemia participants: 2 RCTs, studying children9 and adults10
(dichotomous outcome; yes/no) with hypoglycemia, and 2 nonrandomized crossover
– Time to resolution of symptoms (critical), defined studies with healthy volunteers.11,12
as the time from the administration of the sugar One RCT9 compared sublingual sugar administration
containing solution until the symptoms resolved (2.5 g of wet sugar under the tongue) with oral adminis-
(continuous outcome) tration (2.5 g of sugar on the tongue) in a specific group
– Blood or plasma glucose concentration at 20 of 42 children between 1 and 15 years of age with clinical
minutes (critical), defined as the glucose con- signs and symptoms of acute malaria or respiratory tract
centration measured 20 minutes after the infections and blood glucose concentrations between 50
administration of the sugar substrate (continu- and 80 mg/dL (2.8–4.4 mmol/L) after overnight fasting.
ous outcome) or as evidence of blood or plasma This study did not include children with severe clinical
glucose elevation at 20 minutes (dichotomous signs and symptoms of hypoglycemia. Blood glucose was
outcome; yes/no) measured every 20 minutes for up to 80 minutes after
S288 October 20, 2020 Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897Singletary et al First Aid: 2020 CoSTR
treatment. The authors reported a significant increase in for indirectness. Table 1 provides a summary of evi-
blood glucose concentrations measured at 20 minutes dence for the Consensus on Science for Methods of
after sublingual sugar administration compared with Glucose Administration.
blood glucose concentrations measured at 20 minutes We did not identify any studies testing the rectal ad-
after oral sugar administration. A significant decrease ministration of glucose.
in the time to resolution of hypoglycemia and a higher
likelihood of resolution of hypoglycemia (ie, reaching a Treatment Recommendations
blood glucose concentration of 90 mg/dL [5.0 mmol/L] We recommend the use of oral/swallowed glucose for
or greater during the study period) at 80 minutes after adults and children with suspected hypoglycemia who
treatment was reported after sublingual sugar adminis- are conscious and able to swallow (strong recommen-
tration, compared with oral sugar administration. No ad- dation, very low-certainty evidence).
verse events were reported in either group. No evidence We suggest against buccal glucose administration
was identified to address resolution of symptoms, time compared with oral/swallowed glucose administration
to resolution of symptoms, or treatment delay. for adults and children with suspected hypoglycemia
Two nonrandomized crossover studies compared buc- who are conscious and able to swallow (weak recom-
cal glucose administration with oral administration.11,12 The mendation, very low-certainty evidence).
first study looked at 16 healthy fasting adult volunteers If oral glucose (eg, tablet) is not immediately avail-
who received 10 glucose spray doses (5 doses to the buccal able, we suggest a combined oral and buccal glucose
mucosa of each cheek, totaling 0.84 g glucose) compared (eg, glucose gel) administration for adults and children
with a 6 g dextrose tablet to be chewed and swallowed.11 with suspected hypoglycemia who are conscious and
In the second study of 7 adults, researchers provided 15 g able to swallow (weak recommendation, very low-cer-
of instant glucose, placed between the teeth and the buc- tainty evidence).
cal mucosa of the cheek of each subject, and compared We suggest the use of sublingual glucose adminis-
results with 15 g of instant glucose to be swallowed. The tration for suspected hypoglycemia for children who
subjects who received buccal glucose were encouraged may be uncooperative with the oral (swallowed) glu-
not to swallow.12 Buccal spray glucose resulted in a lower cose administration route (weak recommendation, very
plasma glucose concentration at 20 minutes after admin- low-certainty evidence).
istration compared with the chewed dextrose tablet,11 and
Justification and Evidence-to-Decision
buccal instant glucose (ie, placed against inside cheek) re-
Downloaded from http://ahajournals.org by on October 28, 2020
Framework Highlights
sulted in fewer participants with an increased blood glu-
The limited evidence available for this review was supple-
cose concentration at 20 minutes.12 Thus, both studies fa-
vored oral/swallowed glucose. No evidence was identified mented by task force discussions and summarized in 3
to address resolution of symptoms, time to resolution of accompanying evidence-to-decision tables (Supplement
symptoms, resolution of hypoglycemia, time to resolution Appendix A-1, evidence-to-decision table for buccal glu-
of hypoglycemia, or any adverse event or treatment delay. cose compared with oral swallowed glucose; Supplement
Finally, 1 RCT with 18 adults with insulin-dependent Appendix A-2, evidence-to-decision table for oral-buccal
diabetes and insulin-induced hypoglycemia compared glucose compared with oral swallowed glucose; Supple-
the oral administration of 15 g of glucose supplied as ment Appendix A-3, evidence-to-decision table for sub-
40 g of a 40% dextrose gel (6 adults), with the oral/swal- lingual glucose compared with oral swallowed glucose).
lowed administration of glucose (either a 15 g glucose The task force recommends the use of oral/swallowed
tablet to be chewed and swallowed without water (6 glucose for adults and children with suspected hypo-
adults), or a solution of 15 g glucose in 150 mL of water, glycemia who are conscious and able to swallow. This
swallowed (6 adults).10 In this study, researchers noted does not imply that in a standard first aid setting, other
that the dextrose gel adhered to the mucosa and was routes such as buccal or sublingual glucose administra-
not completely swallowed; for this reason, this adminis- tion cannot be used, but it does suggest that oral/swal-
tration form is labeled as combined oral and buccal mu- lowed glucose be the initial choice in awake adults and
cosal administration in this review. At 20 minutes or less children who are able to swallow. No identified studies
after the glucose administration, no improvement was compared sublingual with buccal administration.
identified for either route in the resolution of symptoms The identified evidence for sublingual glucose admin-
or in plasma glucose concentration. No evidence was istration comes from only 1 study in a group of children
identified to address time to resolution of symptoms, with clinical signs of acute malaria or respiratory tract
resolution of hypoglycemia, time to resolution of hypo- infections. Sublingual administration is favored in this
glycemia, or any adverse event or treatment delay. specific population, but whether the results are appli-
All evidence was of low to very low certainty. All cable in a wider population is uncertain. Therefore, the
studies were downgraded for risk of bias and impreci- task force suggests the use of sublingual administration
sion. The nonrandomized trials were also downgraded of glucose for resource-limited settings in populations
Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897 October 20, 2020 S289Singletary et al First Aid: 2020 CoSTR
Table 1. Summary of Studies of Methods of Glucose Administration
Participants
Intervention: (Number of Certainty of
Outcomes Comparison Studies) RR (95% CI) Evidence (GRADE) Risk With Control Risk With Intervention
Resolution of Combined oral and 18 (1) 10
0.36 (0.12 to 1.14) Very low 917 per 1000 330 per 1000 (110 to
symptoms within 20 buccal versus oral/ 1000)
min (critical) swallowed glucose
administration
Blood or plasma Sublingual 42 (1)9 Very low The mean blood/ The MD was 17 mg/dL
glucose concentration versus oral/ plasma glucose (0.94 mmol/L) higher
at 20 min (critical) swallowed glucose concentration at 20 (4.4 mg/dL [0.24 mmol/L]
administration min was 76 mg/dL higher to 29.6 mg/dL
(4.2 mmol/L) [1.64 mmol/L] higher)
Buccal versus oral/ 16 (1)11 Very low The mean blood/ The MD was 14.4 mg/dL
swallowed glucose plasma glucose (0.79 mmol/L) lower (17.5
administration concentration at 20 mg/dL [0.97 mmol/L]
min was 112 mg/dL lower to 11.4 mg/dL
(6.16 mmol/L) [0.63 mmol/L] lower)
Increased blood Buccal versus oral/ 7 (1)12 0.07 (0.00 to 0.98) Very low 1000 per 1000 70 per 1000 (0 to 980)
glucose at 20 min swallowed glucose
(critical) administration
Resolution of Sublingual 42 (1)9 1.26 (0.91 to 1.74) Very low 467 per 1000 205 per 1000 (44 to 983)
hypoglycemia within versus oral/
20 min (important) swallowed glucose
administration
Resolution of 2.10 (1.24 to 3.54) Very low 733 per 1000 14 per 1000 (0 to 252)
hypoglycemia within
80 min (important)
Time to resolution Sublingual 42 (1)9 Very low The mean time The MD was 51.5 min
of hypoglycemia versus oral/ to resolution of lower
(important) swallowed glucose hypoglycemia was (58 min lower to 45 min
administration 80 min lower)
Adverse events Sublingual 42 (1)9 Very low No adverse events were reported in either group
(important) versus oral/
Downloaded from http://ahajournals.org by on October 28, 2020
swallowed glucose
administration
GRADE indicates Grading of Recommendations, Assessment, Development, and Evaluation; MD, mean difference; and RR, relative risk.
with suspected hypoglycemia where there is concern Dietary Sugars for Treatment of
for the ability to follow commands and swallow. Hypoglycemia (FA 795: EvUp)
One study evaluated the use of glucose gel placed
This EvUp was performed to identify any relevant evi-
on the buccal mucosa and then swallowed. It was ob-
dence published after the most recent SysRev of di-
served that the gel adhered to the oral mucosa; there-
etary sugars for the treatment of hypoglycemia7 and
fore, the task force elected to consider this as a com-
the 2015 First Aid Task Force findings.5,6 This EvUp (see
bined oral and buccal route. The task force recognizes
Supplement Appendix C-1) identified no evidence to
that the findings from this single study are likely unique justify a new SysRev or consider a change in the 2015
to glucose gel and may not be extrapolated to other treatment recommendation about dietary sugars for
forms of glucose such as sprays or pastes administered treatment of hypoglycemia.
buccally and swallowed.
Population, Intervention, Comparator, Outcome,
Knowledge Gaps Study Design, and Time Frame
Research is needed to evaluate the benefits and risks • Population: Adults and children with symptomatic
of different glucose administration routes in adults and hypoglycemia
children with a diminished level of consciousness who • Intervention: Administration of dietary forms of
are not able to swallow, particularly when advanced sugar
care is unavailable such as in rural or wilderness set- • Comparator: Standard dose (15–20 g) of glucose
tings. The use of different forms of sugar, such as tablets
sprays, pastes, or gels, should be further investigated. • Outcome: Time to resolution of symptoms, com-
Additional high-certainty studies are needed to eval- plications, blood glucose level after treatment,
uate outcomes after enteral treatment, such as mortal- hypoglycemia (defined as the persistence of
ity, hospital discharge, or need for hospitalization. symptoms [yes/no] or recurrence of symptomatic
S290 October 20, 2020 Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897Singletary et al First Aid: 2020 CoSTR
hypoglycemia for more than15 minutes after treat- • Comparator: Another cooling technique (or com-
ment), hospital length of stay bination of techniques) appropriate for first aid; for
• Study design: RCTs and nonrandomized stud- case series, there will be no comparator or control
ies (non-RCTs, interrupted time series, controlled group; studies without a comparison group will be
before-and-after studies, cohort studies) were eli- described narratively
gible for inclusion; unpublished studies (eg, con- • Outcome: Mortality and rate of body temperature
ference abstracts, trial protocols) were excluded reduction (°C/min or °C/h) were ranked as critical
• Time frame: All years and all languages were outcomes. Clinically important organ dysfunction,
included as long as there was an English abstract. adverse effects (eg, overcooling, hypothermia,
We reran the existing search strategy on June 25, injury), and hospital length of stay were ranked as
2019. important outcomes.
• Study design: RCTs and nonrandomized stud-
Treatment Recommendations ies (non-RCTs, interrupted time series, controlled
This treatment recommendation (below) is unchanged before-and-after studies, cohort studies), case
from 2015.5,6 series of 5 or more were eligible for inclusion.
We recommend that first aid providers administer Case series cannot provide high-level evidence,
glucose tablets for treatment of symptomatic hypogly- particularly without a comparator group; how-
cemia in conscious adults and children (strong recom- ever, they provide direct evidence about hyper-
mendation, low-quality evidence). thermic patients in comparison with the indirect
We suggest that if glucose tablets are not available, vari- evidence derived when using healthy volunteers.
ous forms of dietary sugars such as Skittles, Mentos©, sug- Unpublished studies (eg, conference abstracts,
ar cubes, jelly beans, or orange juice can be used to treat trial protocols) were excluded.
symptomatic hypoglycemia in conscious adults and chil- • Time frame: All years and all languages were
dren (weak recommendation, very low-quality evidence). included; unpublished studies (eg, conference
There is insufficient evidence to make a recommen- abstracts, trial protocols) were excluded. Literature
dation on the use of whole milk, cornstarch hydroly- search was updated July 11, 2019.
sate, and glucose solution, or glucose gels as compared • PROSPERO Registration: CRD42019128445
with glucose tablets for the treatment of symptomatic Consensus on Science
Downloaded from http://ahajournals.org by on October 28, 2020
hypoglycemia.5,6 The SysRev identified 12 different interventions for cool-
ing. Most of the included studies that compared cooling
Cooling of Heatstroke and Exertional techniques involved small groups of healthy adults with
exertional hyperthermia, providing indirect evidence to de-
Hyperthermia (FA 1548: SysRev) termine the effectiveness of cooling techniques for heat-
Rationale for Review stroke. The direct evidence about cooling for heatstroke
This topic was prioritized for review by the First Aid Task was based on both cohort studies and case series. The
Force based on (a) the importance of the problem, (b) included studies used core temperature measurements
increased number of extreme heat events (heat waves) (eg, rectal and esophageal). For all studies, passive cool-
worldwide, (c) number of major sporting events held in ing was by conduction without a heat source or an active
hot climates, and (d) the potential for increased survival cooling intervention. All other methods of cooling (see
and morbidity associated with heatstroke with the use Table 2) that actively remove heat from a patient’s body
of rapid cooling. The SysRev was completed in 2020.13 were considered active cooling. Cooling by water immer-
sion was conducted in a variety of shallow inflatable, rigid
Population, Intervention, Comparator, Outcome, or semirigid tubs with the person’s whole body placed in
Study Design, and Time Frame the tub with water covering the torso or up to the neck.
• Population: Adults and children (all ages) with For the critical outcome of mortality (with the ex-
heatstroke or exertional hyperthermia; Heatstroke ception of ice-water immersion) and the important
included both exertional and nonexertional (clas- outcomes of clinically important organ dysfunction, ad-
sic) forms; exertional hyperthermia was defined verse events, and hospital length of stay, there were no
as a core body temperature above 40°C occurring comparator studies evaluating any cooling techniques.
during athletic or recreational activity and influ- A summary of the outcome mean weighted cooling
enced by exercise intensity, environmental condi- rate by method is found in Table 2.
tions, clothing, equipment, and individual factors Many studies of cooling techniques failed to show a
• Intervention: Any cooling technique (or combina- significant mean difference in (MD) rate of cooling; these
tion of techniques) appropriate for first aid (con- are summarized in Table 3. The following text summariz-
duction, evaporation, convection, or radiation) es the studies where comparison of cooling techniques
Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897 October 20, 2020 S291Singletary et al First Aid: 2020 CoSTR
Table 2. Mean Weighted Cooling Rate (°C/min) by Cooling Method
Weighted
Cooling Method Average* Variance Standard Deviation Min–Max References
Ice-water immersion (1°C–5°C water), n=111 0.20 0 0.07 0.14–0.35 a14–20
Temperate water immersion (20°C–26°C water), n=47 0.16 0.02 0.13 0.06–0.41 b17,20–23
Cold-water immersion (14°C–17°C water), n=110 0.14 0.03 0.18 0.04–0.62 c14,20–32
Colder-water immersion (9°C–12°C), n=59 0.14 0 0.07 0.04–0.25 d 20,23,29–31,33
Commercial cold packs n=41 0.14 0.01 0.12 0.03–0.17 e34–36
Shower (20°C) n=17† 0.07 - 0.03 - f37
Ice sheets (3°C) and towels n=47 0.06 0 0.01 0.05–0.06 g24,33,38
Hands and feet cold-water immersion (16°C–17°C), n=62 0.05 0 0.05 0.02–0.16 h24,29,39–42
Cooling vests and jackets n=81 0.04 0 0.01 0.02–0.05 i39,43–47
Cold intravenous fluids (4°C) n=17 0.04 0 0.01 0.06–0.07 j36,48
Passive cooling (20°C–39°C ambient) n=391 0.04 0 0.03 –0.01 to 0.12 k14–16,18,19,22,24,25,27–
32,34,35,37–42,44–47,49–53
Fanning n=9† 0.04 - 0 - l39
Hand-cooling devices n=29 0.03 0 0.01 0.02–0.04 m46,49,53
Evaporative cooling n=50 0.03 0 0.03 –0.01 to 0.06 n24,34,36,52
Note: All are active cooling techniques with the exception of passive cooling.
*Rounded to 2 decimal places.
†Unweighted.
demonstrated superiority of 1 technique compared with evidence (downgraded for risk of indirectness) from 3
another. non-RCTs29–31 recruiting 30 adults with exertional hy-
perthermia. The authors reported a faster rate of core
Cold-Water Immersion (14°C–15°C/57.2°F–59°F)
body temperature reduction associated with the use
For the critical outcome of rate of core body tempera-
of colder-water immersion of the torso compared with
Downloaded from http://ahajournals.org by on October 28, 2020
ture reduction, we identified low-certainty evidence
passive cooling (MD, 0.11°C/min; 95% CI, 0.07–0.15).
(downgraded for risk of inconsistency and indirectness)
Moderate-certainty evidence (downgraded for risk of
from 7 non-RCTs comparing cold-water immersion
indirectness) from 1 non-RCT23 recruiting 4 adult sub-
(14°C–15°C/57.2°F–59°F) of the torso with passive cool-
jects with exertional hyperthermia also demonstrated a
ing,14,22,24,25,27,28,32 recruiting 143 adults with exertional
faster rate of core body temperature reduction associ-
hyperthermia. Researchers reported a faster rate of body
ated with the use of “colder” water immersion of the
temperature reduction associated with cold-water im-
torso, compared with temperate water (23.5°C/74.3°F)
mersion of the torso compared with passive cooling (MD
immersion (MD, 0.08°C/min, 95% CI, 0.02–0.14).
range from 0.01°C/min–0.10°C/min). The substantial
heterogeneity across studies precluded pooled estimate Ice-Water Immersion (1°C–5°C/33.8°F–41.0°F)
of the MD in rate of core body temperature reduction for For the critical outcome of mortality, we identified very
all studies evaluating cold-water immersion. low-certainty evidence (downgraded for risk of impre-
cision) from 1 small observational cohort study54 of 23
Cold-Water Immersion of Hands and Feet (10°C–17°C/
adults with exertional heatstroke, comparing the prehos-
50.0°F–62.6°F)
pital use of ice-water immersion of the torso plus the
For the critical outcome of rate of core body tem-
administration of intravenous 0.9% normal saline at am-
perature reduction, we identified moderate-certainty
bient temperature compared with the use of ice bags ap-
evidence (downgraded for risk of indirectness) from
plied to the axilla. There were no deaths in either group.
6 controlled trials24,29,39–42 recruiting 62 adults with ex-
For the critical outcome of rate of core body temper-
ertional hyperthermia. These studies reported a faster
ature reduction, we identified low-certainty evidence
rate of core body temperature reduction with the use
(downgraded for risk of inconsistency and indirectness)
of cold-water immersion of the hands and/or feet com-
from 4 non-RCTs14,16,18,19 recruiting 54 adults with ex-
pared with passive cooling (MD, 0.01°C/min; 95% CI,
ertional hyperthermia and low-certainty evidence from
0.01–0.01).
1 prehospital observational cohort study15 enrolling
Colder-Water Immersion (9°C–12°C/48.2°F–53.6°F) 21 adult distance runners with exertional heatstroke.
For the critical outcome of rate of core body tem- These studies reported a faster rate of core body tem-
perature reduction, we identified moderate-certainty perature reduction associated with the use of ice-water
S292 October 20, 2020 Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897Singletary et al First Aid: 2020 CoSTR
Table 3. Cooling Techniques With Comparisons Not Showing a Finally, we identified low-certainty evidence from 1
Significant Mean Difference in Cooling Rate small observational cohort study54 of 23 adults with ex-
Cold-water immersion of the torso compared with temperate-water ertional heatstroke. This study reported a faster rate of
immersion of the torso (20°C–26°C/68°F–78.8°F)21,22,26 core body temperature reduction associated with the
Cold-water immersion (14°C/57.2°F) of the torso compared with the use use of ice-water torso immersion plus administration
of colder-water immersion (8°C/46.4°F)26
of intravenous 0.9% normal saline compared with use
Cold-water immersion (14°C/57.2°F) of the torso compared with ice-water of ice packs to the axilla (MD, 0.06°C/min; 95% CI,
immersion (2°C–5°C/35.6°F–41°F) of the torso14,26
0.01–0.11).
Colder-water immersion (9°C/48.2°F) up to the iliac crest compared with
passive cooling50 Evaporative Cooling and Alternative Cooling Devices
Colder-water immersion (10°C–12°C/50.0°F–53.6°F) of the hands/feet We identified several studies evaluating evaporative
compared with the use of colder-water immersion of the torso29 cooling (with use of mist and fan or fan alone), ice
Evaporative cooling compared with passive cooling34,52 sheets, hand-cooling devices, cooling vests and jack-
Evaporative cooling compared with use of ice packs applied to the neck, ets, and reflective blankets that identified no significant
axilla, and groin34,36 MD in cooling rates compared with alternative cooling
Evaporative cooling compared with the use of commercial ice packs methods. These studies are also included in Table 3.
applied to the whole body34
Evaporative cooling combined with the use of commercial ice packs to the Commercial Ice Packs
neck, axilla, and groin compared with passive cooling34 and evaporative For the critical outcome of rate of core body tem-
cooling alone34 perature reduction, we identified moderate-certainty
Evaporative cooling compared with the administration of intravenous evidence (downgraded for risk of indirectness) from 1
0.9% normal saline at 20°C/68.0°F36
non-RCT35 recruiting 10 adults with exertional hyper-
Ice-sheet application (bed sheets soaked in ice water kept at 3°C/37.4°F) thermia. This small study reported a faster rate of core
and towels soaked in ice water kept at 14°C/57.2°F, respectively, to the
body compared with passive cooling24,38 body temperature reduction associated with the use of
Ice-sheet application (sheets soaked in ice and water at 5°C–10°C/41.0°F–
commercial ice packs to the facial cheeks, palms, and
50°F) to the body compared with colder-water immersion (5°C– soles compared with passive cooling (MD, 0.18°C/min;
10°C/41.0°F–50°F)33 95% CI, 0.12–0.24).
Commercial ice packs to the neck, groin, and axilla compared with passive We identified moderate-certainty evidence (down-
cooling34,35 graded for risk of indirectness) from 1 controlled trial35
Downloaded from http://ahajournals.org by on October 28, 2020
Commercial ice packs to the whole body compared with passive cooling34 recruiting 10 adults with exertional hyperthermia that
Fanning alone compared with passive cooling24,39 reported a faster rate of core body temperature reduc-
Hand-cooling devices compared with passive cooling46,49,53 tion with the use of commercial ice packs to the fa-
A commercial cooling jacket compared with passive cooling44,46 cial cheeks, palms, and soles compared with the use of
commercial ice packs applied to the neck, groin, and
Various cooling vests compared with passive cooling24,39,44,45,47
axilla (MD, 0.13°C/min; 95% CI, 0.09–0.17).
Reflective blankets compared with passive cooling51
Administration of 2 L of intravenous 0.9% normal saline at 20°C/68°F over Cold Shower (20.8°C/69.4°F)
20 minutes compared with the use of ice packs to the neck, axilla, and For the critical outcome of rate of core body tempera-
groin36
ture reduction, we identified moderate-certainty evi-
Administration of 2 L of cold (4°C/39.2°F) intravenous 0.9% normal dence (downgraded for risk of indirectness) from 1 non-
saline over 30 minutes compared with 2 L of intravenous normal saline at
22°C/71.6°F48 RCT37 recruiting 17 adults with exertional hyperthermia
that reported a faster rate of core body temperature
reduction associated with the use of cold showers com-
immersion of the torso (1°C–5°C/33.8°F–41.0°F) com- pared with passive cooling (MD, 0.03°C/min; 95% CI,
pared with passive cooling (MD range from 0.06°C– 0.01–0.05).
0.23°C/min). The high heterogeneity across studies Intravenous Fluids
precluded calculation of a pooled estimate of the dif- With the exception of the single study of ice-water im-
ference in mean rates of body temperature reduction. mersion, for the critical outcome of mortality and the
We also identified moderate-certainty evidence important outcomes of clinically important organ dys-
(downgraded for risk of indirectness) from 2 prehospi-
function, adverse events, and hospital length of stay,
tal non-RCTs17,26 recruiting 27 adults with exertional hy-
there were no comparator studies evaluating any of the
perthermia. These studies reported a faster rate of core
previously mentioned cooling techniques.
body temperature reduction associated with the use of
ice-water torso immersion (2°C/35.6°F) compared with Treatment Recommendations
temperate-water torso immersion (20°C–26°C/68.0°F– For adults with exertional hyperthermia or exertional
78.8°F) (MD, 0.14°C/min; 95% CI, 0.09–0.18). heatstroke:
Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897 October 20, 2020 S293Singletary et al First Aid: 2020 CoSTR
We recommend immediate active cooling using With the exception of case series, there were no
whole-body (from the neck down) water-immersion studies that evaluated cooling techniques for exertional
techniques (1°C–26°C/33.8°F–78.8°F) until a core heatstroke. The high morbidity associated with heat-
body temperature of less than 39°C/102.2°F is reached stroke creates ethical restraints to using a nontreatment
(weak recommendation, very low-certainty evidence). or nonaggressive treatment comparison. In addition,
We recommend that where water immersion is not none of the included studies evaluated cooling tech-
available, any other active cooling technique be initi- niques in children.
ated (weak recommendation, very low-certainty evi- We noted that there is wide variability in cooling
dence). methods used across different regions and in different
We recommend immediate cooling using any active settings. Some studies demonstrated feasibility of pro-
or passive technique available that provides the most viding whole-body (from the neck down) cold-water
rapid rate of cooling (weak recommendation, very low- immersion using relatively inexpensive “fit for purpose”
certainty evidence) equipment or improvised materials, such as inflatable
For adults with nonexertional heatstroke, we can- children’s pools or tubs in most settings.
not make a recommendation for or against any specific The First Aid Task Force expert consensus opinion was
cooling technique compared with an alternative cool- that passive cooling (eg, moving the person to a cooler
ing technique. environment) is an essential part of the initial manage-
For children with exertional or nonexertional heat- ment of exertional hyperthermia and heatstroke. How-
stroke, we cannot make a recommendation for or ever, it is a slower cooling method compared with most
against any specific cooling technique compared with other studied cooling modalities.
an alternative cooling technique. Given the clinical consequences of delayed cooling
for heatstroke, the task force discussed and agreed that
Justification and Evidence-to-Decision
methods to measure core body temperature should
Framework Highlights
be available in first aid settings where there is a high
In making these recommendations, the First Aid Task
risk of encountering heatstroke, such as sports events,
Force considered the following points (see Supplement
particularly when high ambient temperatures with high
Appendix A-4 for the evidence-to-decision table):
humidity are anticipated.31,54
Heat stroke is an emergent condition characterized
The task force recognizes that the optimal im-
by severe hyperthermia (>40°C/104°F) and organ dys-
mersion time to reduce core temperature to below
Downloaded from http://ahajournals.org by on October 28, 2020
function, typically manifested by central nervous system
39oC/102.2°F is unknown. We considered that even in
dysregulation. The target temperature of 39°C/102.2°F
the absence of core temperature measurement, the use
was selected because it most closely matched the tar-
of water immersion, if available, should be continued
get temperature of the evaluated published research
until symptoms resolve or a reasonable amount of time,
on cooling for heat stroke and avoids overcooling to a
such as 15 minutes, has passed, as benefit from wa-
hypothermic state.20
ter immersion is more likely than harm. To arrive at the
The most rapid cooling was achieved using whole-
15-minute duration, the task force created scenarios
body (from the neck down) immersion in water with
with different initial temperatures and different rates
temperatures of 1°C–26°C/33.8°F–78.8°F. While there
of cooling in an attempt to strike a balance between
was heterogeneity in cooling rates across different wa-
likely benefits and potential harms. Included studies did
ter temperatures, colder water temperatures were asso-
not report significant hypothermia or thermal injuries
ciated with faster cooling rates. Cooling rates achieved
during cold-water immersion across the recommended
with water-immersion techniques were faster than
temperature ranges.
other active cooling modalities such as commercial ice
Combinations of techniques associated with slower
packs, cold showers, evaporative cooling, ice sheets
cooling rates may result in an overall faster cooling rate
and towels, fanning, evaporative cooling, cooling vests,
than any of the techniques used alone, although this
and jackets. However, because confidence intervals
has not been studied.
overlap for most of the mean weighted cooling rates
The task force recognizes that the time required to
for cooling techniques studied, we are unable to pro-
cool a person with heatstroke or exertional hyperther-
vide a rank order list. A graph in Supplement Appendix
mia will vary with body size, age, and additional fac-
A-4 displays trends in mean weighted cooling rates for
tors. A treatment recommendation for specific cooling
cooling techniques evaluated.
duration could not be made in the absence of further
The evidence summary consistently reports core
evidence.
body temperature as measured rectally. The unavailabil-
ity of core rectal temperature measurement should not Knowledge Gaps
preclude initiation of whole-body cold-water immer- • There are no prospective comparative studies of
sion if available. cooling techniques for adults and children with
S294 October 20, 2020 Circulation. 2020;142(suppl 1):S284–S334. DOI: 10.1161/CIR.0000000000000897You can also read
