Cooling Protocol Feasible, Safe in Acute Stroke Patients

Download this article's Factoid (PDF & PPT for Gold Subscribers)

A controlled hypothermia method that has been used successfully in cardiac arrest patients is feasible and relatively safe in patients with acute stroke, according to a study published online January 16, 2014, ahead of print in Stroke. Inducing mild hypothermia in awake patients after thrombolysis also showed hints of being neuroprotective.

Between October 2007 and May 2011, Katja Piironen, MD, of Helsinki University Central Hospital (Helsinki, Finland), and colleagues randomized 36 patients with acute ischemic stroke and a median National Institutes of Health Stroke Scale score of 9 to the hypothermia protocol (n = 18) or standard care (n = 18) within 6 hours of symptom onset. All patients presented to an emergency department and received tPA.

The hypothermia protocol involved cooling blankets wrapped around the patient’s chest, waist, and limbs, in addition to a temperature management system that uses surface cooling and cold saline infusion (Criticool, Mennen Medical Group, Israel). The target temperature of the cooling device was lowered gradually until core temperature reached 35° C to 35.5° C and was then set to 34.5° C. For the induction of hypothermia, 2,000 mL of cold saline was infused within 2 hours. Shivering was controlled by administration of dexmedetomidine (median 0.38 μg/kg/h), meperidine (median 7.0 mg/h), and buspirone (median 35 mg/d) and by increasing the target temperature temporarily.

Safety, Efficacy Demonstrated

The median time from symptom onset to initiation of hypothermia was 6 hours (range, 4.5-6.5). In the hypothermia group, 15 of 18 patients (83%) reached the primary outcome of a core temperature of less than 36° C for more than 80% of the 12-hour cooling period. Sixteen (89%) patients reached < 35.5° C in a median time of 10 hours (range, 7-16 hours) from symptom onset, spent 10.5 hours (range, 1-17 hours) in hypothermia, and were back to normothermia in 23 hours (range, 15-29 hours).

Among the 3 patients who failed to reach the primary outcome, 1 had severe sleep apnea, 1 had a suspected malfunction of the cooling device, and the third patient had uncontrolled shivering, which resolved only with constant meperidine infusion.

While adverse events including bradycardia, mild hypotension or hypertension, shivering, and mild electrolytic disturbances were more frequent in the hypothermia group than the control group, most were not clinically important.

Severe adverse events also were more common in the hypothermia vs control group (19 vs 12). Additionally, 8 patients in the hypothermia group developed hypoxemia at some point during treatment (vs 1 patient in the control group), and 13 (vs 7 controls) were treated with antibiotics. There were no differences between the groups in brain edema formation or hemorrhagic transformation on follow-up CT.

At 3 months, no differences in favorable outcome (modified Rankin Scale score = 0-2; P = 0.298) were seen between the hypothermia and control groups. However, poor outcome (modified Rankin Scale score = 4-6) was twice as common in the control group (44% vs 22%; P = 0.157).

Potential for Expanded Use

Two previous studies—COOL AID II and ICTuS-L—looked at cooling in awake acute stroke patients. But unlike the current study, those trials used an endovascular cooling device, the study authors note. Although surface cooling takes longer than the endovascular device, they say it “is faster and easier to use and can be used by well-trained nurses, and the cooling pads can be installed during the tPA infusion with no risk of device-related hematomas.”

Furthermore, Dr. Piironen and colleagues say, although they used fairly strict inclusion criteria that apply only to a small proportion of patients with stroke, expanding the protocol to include patients with contraindications to thrombolysis “would make the hypothermia treatment available for a larger stroke population.”

Study Details

Baseline characteristics of the randomized groups were similar except for higher rates of A-fib and systolic BP in the hypothermia group.

Patients randomized to the control group were treated according to the institution’s guidelines; additionally, cold infusions, physical cooling, paracetamol, and meperidine were given to keep the core temperature at less than 37.5° C.

 

---

Source:
Piironen K, Tiainen M, Mustanoja S, et al. Mild hypothermia after intravenous thrombolysis in patients with acute stroke: A randomized controlled trial. Stroke. 2014;Epub ahead of print.

 

 

Related Stories:

• Two Trials Look at Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Patients
• Cooling, PCI Improves Long-term Outcomes for Cardiac Arrest Survivors