Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II)

doi:10.1016/j.resuscitation.2012.09.034

Resuscitation

Volume 84, Issue 3, March 2013, Pages 319-325

https://doi.org/10.1016/j.resuscitation.2012.09.034 Get rights and content

Abstract

Aim of the study

Hypothermia exerts profound protection from neurological damage and death after resuscitation from circulatory arrest. Its application during concomitant cardiogenic shock has been discussed controversially, and still hypothermia is used with reserve when haemodynamic parameters are impaired. On the other hand hypothermia improves force development in isolated human myocardium. Thus, we hypothesized that hypothermia could beneficially affect cardiac function in patients during cardiogenic shock.

Methods

14 Patients, admitted to Intensive Care Unit for cardiogenic shock under inotropic support, were enrolled and moderate hypothermia (33 °C) was induced for either one (n = 5, short-term) or twenty-four (n = 9, mid-term) hours.

Results

12 patients suffered from ischaemic cardiomyopathy, 2 were female, and 6 were included after cardiac arrest and resuscitation. Body temperature was controlled by an intravascular cooling device. Short-term hypothermia consistently decreased heart rate, and increased stroke volume, cardiac index and cardiac power output. Metabolic and electrocardiographic parameters remained constant during cooling. Improved cardiac function persisted during mid-term hypothermia, but was reversed during re-warming. No severe or persistent adverse effects of hypothermia were observed.

Conclusion

Moderate Hypothermia is safe and feasable in patients during cardiogenic shock. Moreover, hypothermia improved parameters of cardiac function, suggesting that hypothermia might be considered as a positive inotropic intervention rather than a risk for patients during cardiogenic shock.

Introduction

Hypothermia has become an established therapeutic concept in the treatment of cardiovascular and neurological diseases. First routinely used in patients undergoing open heart surgery¹ and neurosurgery,² moderate hypothermia has meanwhile been shown to exhibit considerable protection from hypoxaemic brain injury after circulatory arrest.3, 4

While feasibility of moderate hypothermia in patients has been proven, there is still some debate about the haemodynamic side effects of hypothermia. Especially in patients with reduced left-ventricular function or even cardiogenic shock potentially detrimental effects of hypothermia have been discussed,⁵ since hypothermia has been observed to decrease cardiac output in healthy animals.6, 7 In consequence, earlier ILCOR and resuscitation guidelines have recommended not to use hypothermia in patients with out-of-hospital cardiac arrest and cardiogenic shock.⁵ However, current registries demonstrate that after cardiac arrest and resuscitation inotropes and/or vasopressors were administered to 77% of patients, and 18% of patients needed further inotropic drugs, vasopressors and/or intra-aortic balloon counter pulsation.⁸

We could previously show in animal experiments and isolated human cardiac muscle that moderate hypothermia exerts calcium-independent positive inotropic effects.7, 9 Thus, we tested the hypothesis that moderate hypothermia is safe to apply and improves cardiac contractile function in patients in cardiogenic shock.

Section snippets

Study design

The study was designed as a prospective, unblinded intervention trial where patients served as their own controls. The study protocol was approved by the ethics committee of the University of Göttingen. The study was carried out in accordance with the Declaration of Helsinki of the World Medical Association and its amendments¹⁰ and European Union guidelines for good clinical practice¹¹ and was led independently of the sponsor. All patients or their immediate relatives, where necessary, gave

Acute effects of cooling on clinical, laboratory and haemodynamic parameters in cardiogenic shock

Moderate hypothermia (33.1 ± 0.1 °C) was reliably achieved in all patients of COOL Shock I, in average within 183 ± 27 min (Table 2). Cooling and moderate hypothermia had no short-term effects on haemoglobin, serum potassium, creatinine and lactate and did not affect global oxygen supply or consumption. In addition, cooling did not change electrocardiographic parameters such as the PQ or the QTc interval (Table 2).

Fig. 2 shows a typical haemodynamic response to cooling, hypothermia, and re-warming in

Discussion

The first major finding of the present study is that the induction of moderate hypothermia up to 24 h is feasible and safe for patients in cardiogenic shock, i.e. the worst condition of acute and chronic heart disease.

This is of crucial interest, since hypothermia has been shown to be the most effective therapeutic intervention to reduce neurological dysfunction and mortality in survivors of cardiac arrest, while at the same time cardiac arrest is in most cases secondary to pre-existing cardiac

Conflicts of interest

None declared.

Acknowledgement

Heat exchange balloon catheters, temperature probes and the cooling system were provided by Radiant Medical.

References (26)

J.P. Nolan et al.
Advancement life support task force of the International Liaison committee on Resuscitation, therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life ssupport task force of the International Liaison Committee on Resuscitation
Resuscitation
(2003)
B.S. Abella et al.
Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey
Resuscitation
(2005)
S. Wolfrum et al.
Mild therapeutic hypothermia after cardiac arrest—a nationwide survey on the implementation of the ILCOR guidelines in German intensive care units
Resuscitation
(2007)
A. Bouwes et al.
Induced hypothermia and determination of neurological outcome after CPR in ICUs in the Netherlands: results of a survey
Resuscitation
(2010)
C. Jacobshagen et al.
Effects of large volume, ice-cold intravenous fluid infusion on respiratory function in cardiac arrest survivors
Resuscitation
(2009)
L.B. Tan
Cardiac pumping capability and prognosis in heart failure
Lancet
(1986)
M. Götberg et al.
Mild hypothermia reduces acute mortality and improves hemodynamic outcome in a cardiogenic shock pig model
Resuscitation
(2010)
D.E. Cameron et al.
Principles of clinical hypothermia
L.A. McIntyre et al.
Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review
JAMA
(2003)
S.A. Bernard et al.
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia
N Engl J Med
(2002)

The Hypothermia after cardiac arrest study group

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

N Engl J Med

(2002)

K.A. Boddicker et al.

Hypothermia improves defibrillation success and resuscitation outcomes from ventricular fibrillation

Circulation

(2005)

H. Post et al.

Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction

Acta Physiol (Oxf)

(2010)

Cited by (48)

Impact of hypothermia on cardiac performance during targeted temperature management after cardiac arrest
2019, Resuscitation
Targeted temperature management (TTM) is a well-accepted neuro-protective intervention in the management of comatose survivors of cardiac arrest (CA). However, the impact of TTM on cardiac performance has not been adequately evaluated.
We reviewed data on consecutive CA survivors undergoing TTM at a quaternary cardiac intensive care unit between January 2015 and June 2017. Enrollment was restricted to cases with invasive hemodynamics (iHDs) at TTM initiation, every 8 h at target temperature (32–34 °C) and at completion of rewarming (>36 °C), unless precluded by mortality. Cardiac index and cardiac index-derived variables were adjusted for a decreased oxygen consumption during hypothermia. We assessed the serial impact of cooling on iHDs and cardiac performance utilizing longitudinal data analysis accounting for the effects of time as surrogate for the expected change from the post arrest syndrome and instituted treatments. A Frank–Starling construct was used to evaluate changes in cardiac contractility.
We evaluated the effects of cooling on iHDs and cardiac performance in 46 CA survivors. Heart rate decreased with cooling (p < 0.001), to return to baseline after rewarming (p = 0.6). Mean arterial pressure and pulmonary wedge pressure decreased by cooling (p < 0.001 for both), with sustained improvement after rewarming (p < 0.001 for both). Systemic vascular resistance was unaffected by hypothermia (p > 0.05). Left stroke work index increased with cooling (p < 0.001), with return to baseline after rewarming (p = 0.6). Cooling was associated with a left-upward shift in the Frank–Starling curve indicative of increased contractility.
Mild hypothermia in CA survivors appears associated to positive changes in iHDs and cardiac performance, including a potential increase in cardiac contractility. Larger studies are needed to conclusively confirm these findings.
Targeted temperature management in the ICU: Guidelines from a French expert panel
2018, Anaesthesia Critical Care and Pain Medicine
Citation Excerpt :
R5.1 We do not suggest considering TTM below 36 °C in patients with cardiogenic shock. Rationale: There were 4 studies that investigated the effects of moderate hypothermia [157–160]. They were retrospective or uncontrolled, and the number of patients included was low.
Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term “targeted temperature management” (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de réanimation de langue française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société francaise d’anesthésie réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société française de médecine d’urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe francophone de réanimation et urgences pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association nationale de neuro-anesthésie réanimation française [ANARLF]), and the French Neurovascular Society (Société française neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts’ opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.
Recent developments in the management of patients resuscitated from cardiac arrest
2017, Journal of Critical Care
Cardiac arrest is the leading cause of death in Europe and the United States. Many patients who are initially resuscitated die in the hospital, and hospital survivors often have substantial neurologic dysfunction. Most cardiac arrests are caused by coronary artery disease; patients with coronary artery disease likely benefit from early coronary angiography and intervention. After resuscitation, cardiac arrest patients remain critically ill and frequently suffer cardiogenic shock and multiorgan failure. Early cardiopulmonary stabilization is important to prevent worsening organ injury. To achieve best patient outcomes, comprehensive critical care management is needed, with primary goals of stabilizing hemodynamics and preventing progressive brain injury. Targeted temperature management is frequently recommended for comatose survivors of cardiac arrest to mitigate the neurologic injury that drives outcomes. Accurate neurologic assessment is central to managing care of cardiac arrest survivors and should combine physical examination with objective neurologic testing, with the caveat that delaying neurologic prognosis is essential to avoid premature withdrawal of supportive care. A combination of clinical findings and diagnostic results should be used to estimate the likelihood of functional recovery. This review focuses on recent advances in care and specific cardiac intensive care strategies that may improve morbidity and mortality for patients after cardiac arrest.
Endothelial function impairment in STEMI patients with out-of-hospital cardiac arrest under therapeutic hypothermia treatment
2017, International Journal of Cardiology
Therapeutic hypothermia (HT) in out-of-hospital cardiac arrest STEMI patients aims to improve their neurological prognosis, but it has been associated with slow coronary flow and cardiac thrombotic events. We sought to serially assess endothelial function during the first 48 h after admission in out-of-hospital cardiac arrest STEMI patients, under therapeutic hypothermia (HT).
From January 2015 to August 2015, eighteen consecutive out-of-hospital cardiac arrest STEMI patients eligible for primary PCI received HT at admission and were included in the study (HT group). During the same time period, eight consecutive patients with large anterior STEMI who received primary PCI but not HT were included as control group. Serial endothelial function by measuring flow-mediated dilatation (FMD) in the brachial artery, biomarkers of endothelial function and oxidative stress were assessed during the first 48 h after admission in both groups.
HT group showed worse FMD as compared to the control group (p < 0.001). Glutathione peroxidase-3 (GPx-3) values were higher in control as compared to HT group (p = 0.019), without any interaction between time of observation and HT (p = 0.864). A significant interaction between time and HT was found in the levels of sVCAM-1, which reached an earlier peak in control than in HT group (p = 0.019). ET-1 values generally increase overtime (p = 0.005), but without any main effect of HT (p = 0.175).
HT is associated with endothelial dysfunction in out-of-hospital cardiac arrest STEMI patients during the first 48 h after admission. This vascular dysfunction may be related to increased oxidative stress due to deficiency of GPx-3 in HT patients.
Electrocardiographic manifestations in three psychiatric patients with hypothermia — Case report
2016, Hellenic Journal of Cardiology
Citation Excerpt :
In mild hypothermia (35°C – 32°C), the electrocardiogram (ECG) is usually normal, but it can show J waves (Osborn waves) in rare situations.3 Osborn waves in inferior and lateral leads, in combination with the appearance of other electrocardiographic manifestations such as prolonged PR and QT intervals, increased QRS complex duration, decreased amplitude of P and T waves and frequent supraventricular arrhythmias, are noted in moderate hypothermia (32°C – 28°C).4–7 In severe hypothermia (<28°C), additional ECG changes such as J waves in all leads, absence of P waves and frequent ventricular arrhythmias may been seen.8–9
Hypothermia occurs when the core body temperature falls below 35°C, which, in severe cases, can lead to electrocardiographic changes. Several conditions that occur in the psychiatric population increase the risk of hypothermia. This risk can be further increased by the use of several classes of medications such as antipsychotics, beta-adrenergic antagonists and benzodiazepines. We report on three psychiatric patients who were admitted for hypothermia and developed electrocardiographic manifestations (sinus bradycardia, QT prolongation and Osborn waves), which completely resolved after treatment.
The optimal hemodynamics management of post-cardiac arrest shock
2015, Best Practice and Research: Clinical Anaesthesiology
Citation Excerpt :
While induced hypothermia has become the standard of care for many CA patients, the present guidelines do not make any explicit recommendations for patients in shock, as shock was an exclusion criterion in previous randomized trials [24]. Recent studies have shown that induced hypothermia improves hemodynamics and may reduce mortality in cardiogenic shock [36–38]. The recently published Target Temperature Management trial (TTM trial) found no differences in mortality or in the composite of poor neurologic function or death between an intervention of 33 and 36 °C.
Patients resuscitated from cardiac arrest develop a pathophysiological state named “post–cardiac arrest syndrome.” Post-resuscitation myocardial dysfunction is a common feature of this syndrome, and many patients eventually die from cardiovascular failure. Cardiogenic shock accounts for most deaths in the first 3 days, when post-resuscitation myocardial dysfunction peaks. Thus, identification and treatment of cardiovascular failure is one of the key therapeutic goals during hospitalization of post-cardiac arrest patients.
Patients with hemodynamic instability may require advanced cardiac output monitoring. Inotropes and vasopressors should be considered if hemodynamic goals are not achieved despite optimized preload. If these measures fail to restore adequate organ perfusion, a mechanical circulatory assistance device may be considered.
Adequate organ perfusion should be ensured in the absence of definitive data on the optimal target pressure goals. Hemodynamic goals should also take into account targeted temperature management and its effect on the cardiovascular function.

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^☆: A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.09.034.

^c: These authors contributed equally to this work.

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Clinical paperModerate hypothermia for severe cardiogenic shock (COOL Shock Study I & II)☆

Abstract

Aim of the study

Methods

Results

Conclusion

Introduction

Section snippets

Study design

Acute effects of cooling on clinical, laboratory and haemodynamic parameters in cardiogenic shock

Discussion

Conflicts of interest

Acknowledgement

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Lancet

Resuscitation

Principles of clinical hypothermia

Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review

JAMA

Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia

N Engl J Med

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

N Engl J Med

Hypothermia improves defibrillation success and resuscitation outcomes from ventricular fibrillation

Circulation

Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction

Acta Physiol (Oxf)

Clinical paper
Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II)☆