Experience with prolonged induced hypothermia in severe head injury

Abstract

Recent prospective controlled trials of induced moderate hypothermia (32⌓34°C) for relatively short periods (24⌓48 h) in patients with severe head injury have suggested improvement in intracranial pressure control and outcome. It is possible that increased benefit might be achieved if hypothermia was maintained for more periods longer than 48 h, but there is little in the literature on the effects of prolonged moderate hypothermia in adults with severe head injury. We used moderate induced hypothermia (30⌓33°C) in 43 patients with severe head injury for prolonged periods (mean 8 days, range 2⌓19 days). Although nosocomial pneumonia (defined in this study as both new chest radiograph changes and culture of a respiratory pathogen from tracheal aspirate) was quite common (45%), death from sepsis was rare (5%). Other findings included hypokalaemia on induction of hypothermia and a decreasing total white cell and platelet count over 10 days. There were no major cardiac arrhythmias. There was a satisfactory neurological outcome in 20 out of 43 patients (47%). Moderate hypothermia may be induced for more prolonged periods, and is a relatively safe and feasible therapeutic option in the treatment of selected patients with severe traumatic brain injury. Thus, further prospective controlled trials using induced hypothermia for longer periods than 48 h are warranted.

Background:

Recent prospective controlled trials of induced moderate hypothermia (32⌓34°C) for relatively short periods (24⌓48 h) in patients with severe head injury have suggested improvement in intracranial pressure control and outcome. It is possible that increased benefit might be achieved if hypothermia was maintained for more periods longer than 48 h, but there is little in the literature on the effects of prolonged moderate hypothermia in adults with severe head injury. We used moderate induced hypothermia (30⌓33°C) in 43 patients with severe head injury for prolonged periods (mean 8 days, range 2⌓19 days).

Results:

Although nosocomial pneumonia (defined in this study as both new chest radiograph changes and culture of a respiratory pathogen from tracheal aspirate) was quite common (45%), death from sepsis was rare (5%). Other findings included hypokalaemia on induction of hypothermia and a decreasing total white cell and platelet count over 10 days. There were no major cardiac arrhythmias. There was a satisfactory neurological outcome in 20 out of 43 patients (47%).

Conclusion:

Moderate hypothermia may be induced for more prolonged periods, and is a relatively safe and feasible therapeutic option in the treatment of selected patients with severe traumatic brain injury. Thus, further prospective controlled trials using induced hypothermia for longer periods than 48 h are warranted.

Introduction

]. These have suggested benefit in intracranial pressure control and outcome when IH was used for 24⌓48 h in the treatment of TBI. Further improvements in outcome may be possible if IH could be used for longer periods, but the effects of prolonged IH have not been well described in the literature. We used IH in 43 patients with severe TBI for periods longer than 48 h and report the incidence of complications of prolonged IH in patients with severe TBI.

Methods

Dandenong Hospital is a 385-bed hospital situated in southeast Melbourne, Victoria, Australia. It services a population of approximately 500000 people. The intensive care unit has seven beds and has an average of 500 admissions per year, 15% of which are because of major trauma (Injury Severity Score >15). Of these, 30% suffer severe closed TBI, defined as a Glascow Coma Scale (GCS) score below 9 at any time after 6 h following injury.

All patients with severe TBI were treated with the following: controlled mechanical ventilation; moderate hypocapnea (partial pressure of carbon dioxide 30 mmHg); avoidance of hypoxia (partial pressure of oxygen >100 mmHg); moderate fluid restriction (15 ml/kg per day dextrose/saline) once normal blood volume had been restored; normothermia (36⌓37°C rectal temperature); and sedation, when required, to control coughing. Mannitol (0.5 g/kg) was given to patients when there was any clinical evidence of deterioration due to cerebral oedema. In addition, other therapies such as muscle relaxants, anticonvulsants and steroids were prescribed on an individual basis.

Monitoring included blood pressure, continuous electrocardiogram, central venous pressure, urine output and rectal temperature. Investigations such as arterial blood gas analysis, chest radiography and electrolyte analysis were performed at least daily. Arterial blood gases were analyzed immediately after collection in the intensive care unit. All arterial blood gas samples were temperature corrected to 37°C. Full blood examination, liver function tests, and specimens for sputum and urine microscopy and culture were collected three times per week. Central venous catheter tips were cultured after removal.

Computed tomography scans of the brain were performed on admission, at 24 h and then as clinically indicated. Intracranial pressure monitoring, using an intraventricular catheter, was only occasionally used before 1996 and routinely since. Patients were nil-by-mouth for 4⌓5 days, after which enteral feeding was attempted. If this had not been established by 7 days, in general, total parental nutrition was instituted.

A group of 43 patients were selected to undergo IH to a rectal temperature of 33°C. This selection was made on an individual basis. In 20 out of 43 patients there was neurological deterioration, despite routine therapy. In 11 out of 43, there had been a failure to improve despite routine therapy. Usually, these patients had shown a significant, but transient improvement after mannitol administration. In 12 out of 43 patients, the decision to institute IH was made pre-emptively when clinical examination, computed tomography scan and/or operative findings suggested that cerebral oedema would be life threatening.

The induction of hypothermia was achieved with surface cooling using ice packs, applied around the head, neck, trunk, groin and axillae. Sedation and muscle relaxation were given as required to suppress shivering until the temperature reached 34°C, after which patients tended to become poikilothermic. Patients were maintained at 31⌓33°C, at which temperature minimal sedation was required, allowing accurate clinical assessment and immediate investigation and therapy of any neurological deterioration.

Patients were rewarmed when there had been a satisfactory improvement in their conscious state, when it was clear that IH had not helped (usually at 5⌓7 days) or when the patient had deteriorated and assessment for brain death was required. Rewarming was passive, and 1°C increase per day was allowed, with immediate recooling if there was clinical neurological deterioration.

Respiratory infection

]. Pneumonia was defined in this study as new chest radiograph opacities, together with a recognized respiratory pathogen cultured from a tracheal aspirate. There were new chest radiograph opacities seen in 22 out of 43 (51%) patients and a sputum pathogen cultured in 28 out of 43 (65%) at some time during IH. Pneumonia, as defined above, occurred in 19 out of 43 (45%). This resolved without complication in 14 of these 43.

Sepsis syndrome

in the blood culture and one with negative blood cultures, but both with new chest radiograph changes. There were no central nervous system, urine or central venous catheter infections identified in the present study.

Cardiac arrhythmias

There were several patients with sinus bradycardia, but all maintained adequate blood pressure without specific therapy. Ventricular ectopy was occasionally seen in association with hypokalaemia. There were no life-threatening cardiac arrhythmias. Osbourne waves were often, but not always, seen on the 12-lead electrocardiogram.

Acid-base changes

shows the pattern in the pH (mean ± standard deviation) over the first 10 days of IH.

Electrolyte changes

shows the potassium levels (mean± standard deviation) for the first 10 days of IH. Of note was the initial hypokalaemia (ie < 3.5 mmol/l) in the first 24 h. Profoundly low potassium (1.2 mmol/l) was unexpectedly found in one patient when ventricular ectopy was noted. This resolved with vigorous intravenous potassium supplementation. No patient developed significant hyperkalaemia on rewarming.

Thrombocytopenia

) at some time during IH. Several of these patients had platelet supplements for surgical procedures, such as tracheostomy or central venous catheter change. No patient suffered a major bleeding complication.

Neutropenia

). Differential counts were rarely requested, so it is not possible in the present study to identify the effects of IH on individual white cell types.

Gastrointestinal tract

A total of 23 out of 43 (53%) patients required total parenteral nutrition, having failed a trial of enteral feeding. A further eight patients tolerated enteral nutrition and 12 were not fed at all during IH.

Delayed wound healing/wound infection

One patient, who had undergone laparotomy on admission, suffered wound dehiscience on day 7 that required resuturing.

Pancreatitis

One patient developed abdominal tenderness and a diagnosis of pancreatitis was made on the basis of a rise in the serum amylase and exclusion of other causes. This settled without consequence.

Discussion

].

]. There was little use of IH in adults with TBI during the 1960s and 1970s until recently, however.

] compared 40 patients with severe TBI who underwent moderate IH (32⌓33°C for 24 h) with 42 patients maintained at normothermia. In IH patients with a GCS score in the range 5⌓8, there were significant improvements in intracranial pressure and outcome, with differences in systemic complications.

< 0.05).

] randomized 22 patients with severe TBI to standard therapy, including normothermia, and 24 patients to similar therapy but including IH (32⌓34°C for 48 h). There were no significant differences between the two groups at entry, but there was a trend towards improved outcome; there was a 16% increase in patients with good outcome in the hypothermic group at 3 months, but this was not significant.

] found that hypothermia increased the rate of wound infection and duration of hospital stay.

] showed that there was no increase in pulmonary complications compared with concurrent control individuals.

] but this was not found in the present study.

].

] found no increase in lactate levels compared with normothermic control individuals.

] and this was observed in one patient in the present series, but resolved without complication.

]. Two patients in the present series required IH for very prolonged periods (18 days and 19 days) because recooling was required.

In the present retrospective study, we are unable to conclude that IH improves outcome. There was patient bias in selection for hypothermia and it is difficult to determine the effects of changes in hyperventilation and fluid therapy that occurred during the course of the study. Nevertheless, we suggest that this study provides evidence that IH for more prolonged periods than 48 h in adults with severe TBI appears to be feasible, provided there is prompt diagnosis and aggressive management of nosocomial pneumonia during maintenance of IH. Overall, sepsis does not appear to carry an unacceptable mortality. The platelet count needs to be regularly measured and, if low, supplemented for surgical procedures such as tracheostomy. The potassium level needs to be carefully monitored and corrected at induction of hypothermia. Because there is a theoretical benefit in the use of IH in TBI, and evidence of safety and efficacy of short-term (24⌓48 h) IH in prospective controlled trials, we conclude that the use of moderate IH (30-33°C) for periods longer than 48 h warrants further randomized prospective controlled trials in adults with severe TBI.

Figures and Tables

Patient Glascow Coma Scale scores (lowest score after 6h)

Clinical profiles of 43 patients

APACHE, Acute Physiology and Chronic Health Evaluation; ICU, intensive care unit.

Mechanism of injury

Glascow Outcome Coma Score at hospital discharge

Biochemical and haematological data

< 0.05, versus day 0.

Keywords

• hypokalaemia
• ileus
• induced hypothermia
• neutropenia
• nosocomial pneumonia
• septic shock
• thrombocytopenia
• traumatic brain injury