On the basis of the published data to date the Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) made the following recommendation on February 2010 with regard to therapeutic hypothermia:
Newly born infants born at term or near-term with evolving moderate to severe hypoxic-ischemic encephalopathy should be offered therapeutic hypothermia.
Whole-body cooling and selective head cooling are both appropriate strategies.
Cooling should be initiated and conducted in neonatal intensive care facilities using protocols consistent with those used in the randomized clinical trials i.e. commence within 6 h, continue for 72 h and rewarm over at least 4 h.
Carefully monitor for known adverse effects of cooling – thrombocytopenia and hypotension.
All treated infants should be followed longitudinally.
Therapeutic hypothermia following intrapartum hypoxia-ischemia. An advisory statement from the Neonatal Task Force of the International Liaison Committee on Resuscitation Resuscitation 2010;81(11):1459-1461
Pre-hospital therapeutic hypothermia might be a good thing, but there may be difficulties in achieving it if the 4 degrees C saline warms up during the infusion. What’s the optimal way of administering it? Czech investigators attempt to answer the question:
Background The cooling efficacy of intravenous administration of cold crystalloids can be enhanced by optimisation of the procedure. This study assessed the temperature stability of different application regimens of cold normal saline (NS) in simulated prehospital conditions.
Methods Twelve different application regimens of 4°C cold NS (volumes of 250, 500 and 1000 ml applied at infusion rates of 1000, 2000, 4000 and 6000 ml/h) were investigated for infusion temperature changes during administration to an artificial detention reservoir in simulated prehospital conditions.
Results An increase in infusion temperature was observed in all regimens, with an average of 8.163.38C (p<0.001). This was most intense during application of the residual 20% of the initial volume. The lowest rewarming was exhibited in regimens with 250 and 500 ml bags applied at an infusion rate of 6000 ml/h and 250 ml applied at 4000 ml/h. More intense, but clinically acceptable, rewarming presented in regimens with 500 and 1000 ml bags administered at 4000 ml/h, 1000 ml at 6000 ml/h and 250 ml applied at 2000 ml/h. Other regimens were burdened by excessive rewarming.
Conclusion Rewarming of cold NS during application in prehospital conditions is a typical occurrence. Considering that the use of 250 ml bags means the infusion must be exchanged too frequently during cooling, the use of 500 or 1000 ml NS bags applied at an infusion rate of $4000 ml/h and termination of the infusion when 80% of the infusion volume has been administered is regarded as optimal.
A Czech study demonstrated effective pre-hospital therapeutic cooling of post-cardiac arrest patients using fairly modest amounts of intravenous saline at 4°C: the administration of 12.6 ± 6.4 mL/kg (1,032 ± 546 mL) of 4°C normal saline led to a tympanic temperature decrease of 1.4 ± 0.8°C (from 36.2 ± 1.5 to 34.7 ± 1.4°C; P < 0.001) in 42.8 ± 19.6 minutes. No ice packs were applied.
Before other emergency medical services adopt this, it should be noted that all these patients were managed in the field by emergency physicians who administered sedatives and neuromuscular blockers. It’s a European thing.
We all like to treat selected post cardiac arrest patients with hypothermia now, but isn’t hypothermia associated with a drop in potassium, which of course can precipitate pesky ventricular dysrhythmias in patients who would really rather not arrest again. Maybe the hypothermia itself is protective against the dysrhythmias?
A study from the Mayo Clinic updates our knowledge of this area:
METHODS: We retrospectively analyzed potassium variability with Therapeutic Hypothermia (TH) and performed correlative analysis of QT intervals and the incidence of ventricular arrhythmia.
RESULTS: We enrolled 94 sequential patients with OHCA, and serum potassium was followed intensively. The average initial potassium value was 3.9±0.7 mmol/l and decreased to a nadir of 3.2±0.7 mmol/l at 10 h after initiation of cooling (p<0.001). Eleven patients developed sustained polymorphic ventricular tachycardia (PVT) with eight of these occurring during the cooling phase. The corrected QT interval prolonged in relation to the development of hypothermia (p<0.001). Hypokalemia was significantly associated with the development of PVT (p=0.002), with this arrhythmia being most likely to develop in patients with serum potassium values of less than 2.5 mmol/l (p=0.002). Rebound hyperkalemia did not reach concerning levels (maximum 4.26±0.8 mmol/l at 40 h) and was not associated with the occurrence of ventricular arrhythmia. Furthermore, repletion of serum potassium did not correlate with the development of ventricular arrhythmia.
CONCLUSIONS: Therapeutic hypothermia is associated with a significant decline in serum potassium during cooling. Hypothermic core temperatures do not appear to protect against ventricular arrhythmia in the context of severe hypokalemia and cautious supplementation to maintain potassium at 3.0 mmol/l appears to be both safe and effective.
Therapeutic hypothermia (TH) has been associated with improved outcomes in term infants who present with moderate hypoxic-ischaemic encephalopathy (HIE). However, in the three major studies the time to initiate cooling was at approximately 4.5 postnatal hours. Many newborns are referred to specialist centres where cooling takes place from outlying hospitals (‘outborn’). It may be the case that earlier initiation of TH could improve outcomes, leading Takenouchi and colleagues to propose a ‘Chain of Brain Preservation’.
‘Given that most infants are outborn, a time sensitive education metaphor termed Chain of Brain Preservation may facilitate early recognition of high risk infants and thus earlier treatment.‘
Aeromedical retrieval specialists in Scotland developed a simple, cheap, effective in-flight cooling protocol using intravenous (IV) cold Hartmann’s solution and chemical cooling packs. Fluids cooled in a fridge (4°C) were transported in an insulated cool box; the patient was sedated, paralysed and intubated, and controlled ventilation started. The patient was then cooled by IV infusion of 30 ml/kg of cold Hartmann’s. Chemical ice packs were activated and placed in the axillae and groin. The time interval between successful resuscitation and the patient being retrieved and flown to an Intensive Care Unit (ICU) was at least 3.5 h. Cooled patients had a mean decrease in body temperature during retrieval compared to patients not cooled (−1.6 °C vs. +0.9 °C, p = 0.005) and a lower body temperature on ICU arrival (34.1 °C vs. 36.4 °C, p = 0.05). Two of the 5 cooled patients achieved target temperature (<34 °C) before ICU arrival. No complications of in-flight cooling were reported.
An Australian randomised controlled trial assessed the effect of pre-hospital cooling (using 2 litres ice cold Hartmann’s) of post-cardiac arrest patients on functional status at hospital discharge. The intervention group were marginally cooler on arrival but did not have improved outcomes.
The authors conclude: In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold intravenous fluid decreased core temperature at hospital arrival but was not shown to improve outcome at hospital discharge compared with cooling commenced in the hospital.
One issue from this study was that relatively short urban pre-hospital transport times meant some patients did not get the full two litres, and some had already received room temperature fluids during the cardiac arrest resuscitation. The authors suggest further study should involved initiating cooling during the arrest. In fact a European study has done just that, using a device call a RhinoChill (a portable transnasal cooling device) to lower temperature during arrest in a randomised controlled trial. This trial showed pre-hospital intra-arrest transnasal cooling is safe and feasible and is associated with a significant improvement in the time intervals required to cool patients.
Percutaneous coronary intervention did not increase the risk of dysrhythmia, infection, coagulopathy, or hypotension associated with therapeutic hypothermia after cardiac arrest. Intensivists and cardiologists should perhaps agree that this adds to existing evidence that the two therapies are not mutually exclusive. Feasibility and safety of combined percutaneous coronary intervention and therapeutic hypothermia following cardiac arrest Resuscitation. 2010 Apr;81(4):398-403
In three randomised controlled trials encompassing 767 infants with hypoxic-ischaemic encephalopathy, induced moderate hypothermia for 72 hours significantly reduced the combined rate of death and severe disability, with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function, with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability and cerebral palsy. The studies used different cooling methods and different target temperatures (33-34 deg C vs 34-35 deg C), suggesting the method of cooling itself is not important as long as therapeutic hypothermia is achieved.
Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data BMJ. 2010 Feb 9;340:c363
Thirty-eight post-cardiac arrest patients were effectively cooled to the target temperature range of 32-34 celsius using intravenous cold saline and ice packs to groin, axillae, and neck. The ice packs were frozen 250 ml saline bags wrapped in pillow cases. If shivering occurred muscle relaxation with rocuronium was used until the target temperature was reached. Interestingly, rebound hyperthermia occurred in 8/34 patients.
Although a small study, these data reassure those of us who induce therapeutic hypothermia without the use of dedicated cooling equipment.
Cold saline infusion and ice packs alone are effective in inducing and
maintaining therapeutic hypothermia after cardiac arrest Resuscitation 2010;81:15–19