Hypothermia | #operation FFICM

Expanded Case Summary by Dr Matthew James Jackson

Clinical Problem

A 55 year old man presented to the ambulance service in cardiac arrest at his home, following a 999 call by his wife. The patient, a lifelong smoker, was receiving anti-hypertensive treatment from his general practitioner; he had taken early retirement due to angina several years ago. Prior to the 999 call he had complained of severe chest pain for approximately 15 minutes and then collapsed. His wife was unable to provide basic life support. The paramedics arrived and commenced cardiopulmonary resuscitation within 6 minutes of notification.

The paramedics secured the airway with a size four Laryngeal Mask Airway, gained intravenous access and applied defibrillator paddles. The initial rhythm was ventricular fibrillation. They performed four cycles of advanced life support administering one dose of adrenaline and amioderone prior to the patient regaining a spontaneous circulation.

Management

On arrival in the resuscitation room, the patient was making no spontaneous respiratory effort; he had a heart rate of 124 bpm and blood pressure of 104/68 mmHg. The emergency physicians intubated the patient and performed baseline investigations. They administer two litres of ice cold saline were administered and summonsed cardiology and critical care to assist with further management.

A joint discussion between the three specialties hypothesised that the presentation was primarily cardiac in nature. However, due to the lack of ST elevation on the ECG and the perceived instability of the patient, he was transported to the Intensive Care Unit for 24 hours of therapeutic hypothermia and ongoing post-arrest care.

Discussion

This patient was admitted prior to recent publications, which now question immediate therapeutic hypothermia following return of spontaneous circulation without a return to consciousness [1, 2]. I chose this particular case in order to explore what my approach to a similar patient would now be. In the remainder of this paper I will review the rationale behind cooling and summarise the large trials which led to the adoption and modified implementation of this concept. In particular I will consider the controversies and knowledge gaps in this field and conclude with my own approach when presented with a similar patient who has not regained consciousness following cardiac arrest.

Cooling is associated with risks and benefits. The risks, include a fall in cardiac output, arrhythmias with a risk of ventricular fibrillation below 28°C, reduced tissue oxygen delivery due to a left-shift in the oxy-haemoglobin dissociation curve, vasoconstriction, and increased blood viscosity and immune-dysfunction. The potential benefits to a brain injured patient include reduced cerebral metabolic rate, reduction in inter-cranial pressure and a reduction in the production of free radicals which have been hypothesised to reduce any reperfusion injury. This balance of risks and benefits provide is the back drop from which randomised trials should be viewed.

Cooling follow cardiac arrest with persistent coma following return of spontaneous circulation became common practice following the publication of two papers in 2002. Bernard and colleagues demonstrated in 77 patients randomised to either 12 hours of hypothermia (33°C) within 2 hours of return of spontaneous circulation or standard care, that treatment was associated with a 5.25 odds ratio of a favourable outcome [3]. In the same issue of the NEJM the Hypothermia after Cardiac Arrest Study Group reported similar findings in 275 patient who were randomised to receive a target temperature of 32-34°C over 24 hours or standard care [4]. In both studies, there were few complications associated with cooling. Both studies exclusively recruited patients out of hospital, in whom the initial rhythm was ventricular fibrillation and excluded patients with what might be considered poor prognosis signs, for example, on-going hypotension. The generalizability of these studies might be questioned when considering that the larger trial screened 3551 but recruited only 275 patients.

Therapeutic cooling was subsequently endorsed by the Resuscitation Council, Cochran and NICE [5, 6]—rapidly becoming a standard of care for this patient cohort. Clinically it was extended to both patients who had arrested in and out of hospital; the initial tight inclusion and exclusion criteria used in the original trials became more liberally applied and then ignored in clinical practice. Simplistically, at the time, it was argued that the hypoxic brain injury was the primary determinant of patients outcome, therefore, factors such as presenting rhythm and place of arrest were probably irrelevant and the patient should be given the best treatment possible. As this practice became mainstream several case-series, with wider, more pragmatic inclusion criteria replicated the results of the original trials [7].

The results of two recent trials have questioned the benefit of therapeutic hypothermia [1, 2]. Both recruited patients who suffered an out of hospital cardiac arrest. The Targeted Temperature Management (TTM) trial recruited 950 patients who were randomly assigned to a targeted temperature of either 33°C or 36°C and failed to show a difference in neurological recovery or survival [2]. The second trial recruited 1359 patients and randomised patients to pre-hospital cooling or standard care, which for most patients involved in-hospital cooling; no difference was seen in patient outcomes [1].

Taken together, these two trials should impact practice. Firstly, the speed of which patients are rendered hypothermic would appear less important than initially thought. From anecdotal experience, alongside the trial data, hyperthermia is rarely a problem prior to admission to the Intensive Care Unit—in fact many patients are admitted with mild hypothermia. Secondly, avoidance of hyperthermia as opposed to aggressive hypothermia, has been proposed as the actual benefit of cooling (although in TTM there was not a standard care group to compare the outcomes of patients who were maintained at 36°C).

The main unanswered question revolves around identifying which patient subgroup will benefit from hypothermia. In the interim period, a further meta-analysis with the inclusion of new data will help guide clinicians. Future trials should treat post-resuscitation syndrome as a heterogeneous group of patients and employ statistical techniques that identify which particular patients benefit from therapeutic hypothermia. A move to conceptualise cooling as a drug, whose dose and duration of use, like other treatment modalities in critical care, is titrated to clinical response is appealing.

Lessons Learnt

Notwithstanding the evidence available at the time, management in this case fixated upon the hypothermic option without giving due consideration to the underlying cause and treatment of this presentation. Recent evidence, alongside older evidence would question this prioritisation; therapeutic hypothermia is not a magic built.

In the light of new evidence, post-resuscitation must now utilise cooling technologies purchased for therapeutic hypothermia to deliver the new paradigm of targeted temperature management. Further evidence, reanalysis and consensus is awaited to guide clinicians to a sub-set of patients who might benefit from lower temperatures. At the time of writing we await a consensus from the International Liaison Committee on Resuscitation and the European Resuscitation Council [8].