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14th October 2022
The value of hypothermic temperature control for unconscious patients following an in-hospital cardiac arrest remains controversial. In guidelines jointly produced by the European Resuscitation Council and the European Society of Intensive Care Medicine, it was recommended that in patients who remain comatose after cardiac arrest, continuous monitoring of core temperature is undertaken for preventing fever. However, the guideline also adds that there was insufficient evidence to recommend for or against temperature control at 32-36 °C or early cooling after cardiac arrest but a recognition of the limited evidence concerning the potential benefit of temperature control after in-hospital cardiac arrest. The evidence of hypothermic temperature control in unconscious patients following an out-of-hospital cardiac arrest is also equivocal, with some data supportive of such control for improving outcomes, whereas other data using a similar cohort, revealing that hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.
For the present study, a team of German researchers undertook a randomised controlled trial to examine the effect of hypothermic temperature control following an in-hospital cardiac arrest (IHCA) on mortality and functional outcome compared with normothermia. The team recruited patients with a Glasgow Coma Scale Score of less than 8 (i.e., unconscious) for longer than 45 minutes after their IHCA. Individuals were eligible irrespective of the initial rhythm or aetiology of the cardiac arrest and randomised 1:1 to hypothermic temperature control with a target range of 32° to 34°C and which was maintained for 24 hours followed by slow re-warming to achieve a target of 37.5°C. In those assigned to normothermia there was no specific range although it was recommended to avoid fever (i.e., a temperature > 37.5°C). All of the patients were followed until 180 days after randomisation and the primary outcome was all-cause mortality after 180 days. Secondary outcomes included in-hospital mortality and favourable functional outcome after 180 days based on the Cerebral Performance Categories (CPC) scale.
Hypothermia temperature control and all-cause mortality
Overall, 242 patients with a mean age of 72.6 years (64% male) were included with 123 randomised to hypothermic temperature control. After 48 hours the average temperature was 34.5° for the intervention group.
By day 180, the mortality rate was 72.5% in the hypothermic group and 71.2% in the normothermic group and this difference was not significant (relative risk, RR = 1.03, 95% CI 0.79 – 1.40, p = 0.82). In-hospital mortality was also not significantly different (RR = 1.11, 95% CI 0.86 – 1.46, p = 0.44).
In addition, after 180 days, a CPC score of 1 or 2 (normal (1) to moderate disability (2)) was achieved for a similar number of patients in the two groups (RR = 1.04, 95% CI 0.78 – 1.44, p = 0.82). In fact, the trial was terminated prematurely because of futility.
The authors concluded that among comatose patients successfully resuscitated from an IHCA, the use of hypothermic temperature control compared to normothermia, did not improve either survival or functional outcome.
Wolfrum S et al. Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial Circulation 2022
1st November 2021
Combining vasopressin and methylprednisolone provides a significantly better chance of return to normal circulation in hospitalised patients experiencing a cardiac arrest compared to placebo. This was the finding of a randomised trial by a team from the Research Center for Emergency Medicine, Aarhus, Denmark. Data on the incidence of in-hospital cardiac arrests in the UK, the annual incidence of in-hospital cardiac arrests has been estimated to be 1 to 1.5 per 1,000 hospital admissions with only around 23% surviving to discharge. Similarly, in the US, around 290,000 adults suffer an in-hospital cardiac arrest every year and again, survival to discharge occurs in only around a quarter of patients.
The drug treatment of cardiac arrest within hospital includes the use of epinephrine, amiodarone or lidocaine although these recommendations are based on studies of patients with cardiac arrests that occur outside of hospital. The use of vasopressin and methylprednisolone in those with cardiac arrest has been previously explored in two studies. The first trial in 2009 was conducted with 100 patients and the authors concluded that combined vasopressin-epinephrine and methylprednisolone during resuscitation improved survival in refractory in-hospital cardiac arrest. A more recent 2013 study, randomised patients to either vasopressin and epinephrine or saline and epinephrine and those in the vasopressin group also received a single dose of methylprednisolone (40 mg). Although the vasopressin and methylprednisolone combination resulted in improved survival to hospital discharge, both the US and European resuscitation guidelines, do not currently recommend this drug combination.
The present Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial, was designed to test whether this combination improved the return to spontaneous circulation in those suffering an in-hospital cardiac arrest. Included patients were required to have at least one dose of epinephrine during a cardiac arrest and the intervention comprised methylprednisolone 40 mg and 20 IU of vasopressin given as soon as possible after the first dose of epinephrine. An additional four doses of vasopressin (20 IU) were permitted after each epinephrine dose and the placebo consisted of 9 mg/mL of sodium chloride from identical ampoules. The primary outcome was the return of spontaneous circulation, i.e., where there was no further need for chest compressions sustained for at least 20 minutes. A key secondary outcome was 30 day survival and survival with a favourable neurological outcome, based on a cerebral performance category (CPC) score of 1 or 2.
A total of 501 patients with a mean age of 71 years (64% male) were included in the final analysis. Overall, 100 patients (42%) in the vasopressin and methylprednisolone group achieved the primary outcome compared to 86 (33%) in the placebo group (risk ratio, RR = 1.30, 95% CI 1.03 – 1.63, p = 0.03). However, 30-day survival was not significantly different (RR = 0.83, 95% CI 0.50 – 1.37, p = 0.48) and there was also no difference in the proportion of patients achieving a CPC scores of 1 or 2.
The authors concluded that while compared to placebo, the combination of vasopressin and methylprednisolone increased the likelihood of a return to spontaneous circulation, there remained uncertainty over whether this treatment resulted in benefit or harm for the longer term survival of patients.