Mild hypothermia in improving multiple organ dysfunction after cardiac arrest

Abstract

BACKGROUND:

Resuscitation after cardiac arrest (CA) with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.

METHODS:

The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the rectum) over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the first 72 hours after recovery of spontaneous circulation (ROSC).

RESULTS:

At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not significantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.

CONCLUSION:

In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.

INTRODUCTION

The morbidity and mortality associated with survival from cardiac arrest remain significant despite recent advances in resuscitation techniques.[1-3] A recent report from North America revealed that only 7.9% of patients with cardiac arrest could survive to hospital discharge.[4] Most of them died from multiple organ dysfunction (MODS). Mild hypothermia is recommended in the current treatment guidelines for brain injury after cardiac arrest.[2, 5,6] The present study aimed to determine whether mild systemic hypothermia could alleviate multiple organ dysfunction after resuscitation from cardiac arrest.

METHODS

Patients

The patients who had been admitted to intensive care unit after recovery of spontaneous circulation from cardiac arrest were eligible for the study. The criteria for inclusion included cardiac arrest, age of more than 18 years, no response to verbal commands after ROSC, and stable electrocardiograph and circulation more than 6 hours after restoration of spontaneous circulation.

Excluded were those if they met any of the following criteria: rectum temperature below 30 °C on admission, MODS before cardiac arrest, response to verbal commands after the return of spontaneous circulation, hypotension (mean arterial pressure, less than 60 mm Hg) for more than 30 minutes after the recovery of spontaneous circulation, and death within 6 hours after ROSC.

Study design

This retrospective cohort study was carried out from January 2002 to January 2010. A total of 112 patients were assessed for eligibility; 63 of these patients didn’t meet the inclusion criteria. Thus, 49 patients were enrolled, with 23 patients assigned to a hypothermia group and 26 to a normothermia group. The base lines of the patients in the two groups were generally similar (Table 1). The indices of different organ injury were compared between the two groups.

Table 1.

Baseline characteristics of the patients

Treatment

All patients received standard intensive care according to a detailed protocol and they were given mechanical ventilation. To prevent shivering, paralysis was induced by intravenous administration of atracurium continuously.

Rectum temperature of the patients was measured. The patients in the normothermia group were placed on a conventional hospital bed, and normothermia was maintained, whereas those in the hypothermia group were cooled to a target temperature of 32 °C to 34 °C using an external cooling device (hypothermic blanket) in order to reach the target rectum temperature within 6 hours after the recovery of spontaneous circulation. The temperature was maintained at 32 °C to 34 °C for 24 to 36 hours from the very begaining of cooling, followed by passive re-warming, and the speed was set at 0.25-0.5 °C/h.

Data collection

Data on cardiac arrest for individual patients were recorded in the Utstein style.[7] The following parameters were observed in all patients: glasgow score, oxygenation index, serum creatinine (SCr), serum total bilirubin (STB), alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CKMB), cardiac troponin I (ctnI), prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count (PLT).

Statistical analysis

Continuous variables were expressed as mean ± SD. Categorical variables were reported as counts and percentages. Primary and secondary outcomes were binary, and the Student’s t test, as appropriate, was used to compare the difference of variables between the hypothermia and normothermia groups. The threshold of statistical significance was set at P<0.05.

RESULTS

Indices of injury of the nervous system

Immediately after recovery of spontaneous circulation, poor results of the nervous system were observed in all of the patients. Seventy-two hours later, however, Glasgow score in the mild hypothermia group was increased, but in the normothermia group decreased (Table 2).

Table 2.

Glasgow score of the patients 72 hours after ROSC (mean ±SD)

Indices of myocardial and pulmonary injury

At 0-1 hour after ROSC, patients in the two groups suffered from myocardial and pulmonary injury, indicating that there were no statistical significances. Ck-MB and CTnI, which show injury of myocardial injury, increased with the time in both groups, but decreased earlier in the mild hypothermia group. Partial pressure of oxygen in artery (PaO₂) / fraction of inspired oxygen (FiO₂) served as the index of pulmonary injury, and PaO₂/FiO₂ was higher in the mild hypothermia group than in the normothermia group (t = 3.5, P = 0.01) (Table 3).

Table 3.

Ck-MB , CTnl and PaO₂/FiO₂ of the patients 72 hours after ROSC (mean ±SD)

Indices of hepatic and renal injury

In the mild hypothermia group, the levels of STB and ALT increased at the first 24 hours and decreased at 24-72 hours, but they were higher than those at 0-1 hour. In the normothermia group, the levels of STB and ALT increased at the first 48 hours and decreased at 48-72 hours, but they were higher than those at 0-1 hour. SCr level was increased within 72 hours, and no significant difference was observed between the two groups (Table 4).

Table 4.

STB, ALT, and Scr of the patients 72 hours after ROSC (mean ±SD)

Indices of blood coagulation injury

PLT decreased within 48 hours after ROSC in both groups; in the mild hypothermia group, PLT was further decreased within 48-72 hours, while in the normothermia group, it was increased. PT and APTT were increased first and then decreased, but they were still higher than those at 0-1 hour (Table 5).

Table 5.

PT, APTT, and PLT of the patients 72 hours after ROSC (mean ±SD)

DISCUSSION

In our patients after recovery of spontaneous circulation from cardiac arrest, systemic cooling made rectum temperature range between 32 °C and 34 °C for 12-24 hours, and decreased injury to the brain, myocardium, liver and lung, compared with standard normothermic life support. However, mild hypothermia damaged the coagulation function. During arrest, blood flow ceases, and cardiac tissues were injured because of anoxia.

It is known that CPR can partially restore the microcirculatory flow. The effects of whole-body ischemia followed by reperfusion activate a systemic inflammatory response.[8-11] Hypothermia can lower the glutamate level and the subsequent production of oxygen free radicals,[12] and post ischemic hypothermia reduces the number of death cells in certain brain regions.[13-15] In the present study, however, patients in the mild hypothermia group did not show any better results of the nervous system because of long-term hypoxia that prevents the brain from recovery. Post-cardiac myocardial dysfunction is common and it can be attributed to myocardial stunning, which is quite variable but reversible.[16-19] Mild hypothermia can inhibit the systemic metabolism and reduce the need of oxygen and the burden of the myocardium.[20,21] Pulmanory or hepatic injury following resuscitation is always caused by inflammatory reaction, which can be reduced by mild hypothermia. However, hypothermia may cause bradycardia and pneumonia, which are easy to be treated.[22]

Hypothermia can cause dieresis and subsequently hypovolemia.[23,24] In the present study, Scr increased in the two groups but there was no significant difference between them. Obviously the effect of hypothermia on renal function was not clear. Recent studies have shown that cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) could early detect renal injury.[25,26] Hence we had to observe the differences in the expression of cystatin C and NGAL between the two groups.

Coagulopathy is the most serious complication of hypothermia, and it may cause death.[22] In this study PLT markedly decreased in the mild hypothermia group but PT and APTT were not prolonged. The mechanism of these changes is unclear.

In patients who have been successfully resuscitated after cardiac arrest, mild hypothermia can decrease multiple organ dysfunction after resuscitation from cardiac arrest although there are side effects.