Laurens L. A. Bisschops

Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study

INTRODUCTION Outcome studies in patients with anoxic-ischemic encephalopathy focus on the early and reliable prediction of an outcome no better than a vegetative state or severe disability. We determined the effect of mild therapeutic hypothermia on the validity of the currently used clinical practice parameters. METHODS We conducted a retrospective cohort study of adult comatose patients after cardiac arrest treated with hypothermia. All data were collected from medical charts and laboratory files and analyzed from the day of admission to the intensive care unit until day 7, discharge from the intensive care unit or death using the Utstein definitions for the registration of the data. RESULTS We analyzed the data of 103 patients. The combination of an M1 or M2 on the Glasgow Coma Scale or absent pupillary reactions or absent corneal reflexes on day 3 was present in 80.6% of patients with an unfavourable and 11.1% of patients with a favourable outcome. The combination of M1 or M2 and absent pupillary reactions to light and absent corneal reflexes on day 3 was present in 14.9% of patients with an unfavourable and none of the patients with a favourable outcome. None of the patients with a favourable outcome had a bilaterally absent somatosensory evoked potential of the median nerve. The value of electroencephalogram patterns in predicting outcome was low, except for reactivity to noxious stimuli. CONCLUSIONS No single clinical or electrophysiological parameter has sufficient accuracy to determine prognosis and decision making in patients after cardiac arrest, treated with hypothermia.

Preserved metabolic coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest.

Objective:Although mild hypothermia improves outcome in patients after out-of-hospital cardiac arrest, the cardiodepressive effects of hypothermia may lead to secondary brain damage. This study was performed to assess the cerebral blood flow, cerebral oxygen extraction, and cerebrovascular reactivity to changes in partial pressure of carbon dioxide in the arterial blood in comatose patients after out-of-hospital cardiac arrest treated with mild hypothermia. Design:Observational study. Setting:Tertiary care university hospital. Patients:Ten comatose patients after out-of-hospital cardiac arrest. Interventions:All patients were cooled to 32–34°C for 24 hrs. Cerebrovascular reactivity to changes in carbon dioxide in the arterial blood was measured after increasing or decreasing the minute ventilation by 20%. Measurements and Main Results:Mean flow velocity in the middle cerebral artery and pulsatility index were measured by transcranial Doppler at 0, 3, 6, 9, 12, 18, 24, and 48 hrs after admission. Jugular bulb oxygenation was measured at the same intervals. Cerebrovascular reactivity to changes in carbon dioxide in the arterial blood was studied on admission to the intensive care unit and at 6, 12, 18, and 24 hrs by measurement of mean flow velocity in the middle cerebral artery and jugular bulb oxygenation. Mean flow velocity in the middle cerebral artery was low (30.3 ± 9.5 cm/sec) on admission and remained relatively stable for the first 24 hrs. After rewarming, it increased to 67.5 ± 33.0 cm/sec at 48 hrs after admission from 30.3 ± 9.5 at admission (p = .009). Jugular bulb oxygenation at the start of the study was 66.2 ± 8.5% and gradually increased to 82.9 ± 4.9% at 48 hrs (p < .001). Regression analysis showed a significant correlation between changes in carbon dioxide in the arterial blood, mean flow velocity in the middle cerebral artery (p < .001) and jugular bulb oxygenation (p < .001). The mean percentage change in mean flow velocity in the middle cerebral artery was 3.6 ± 2.9% per 1-mm Hg change of carbon dioxide in the arterial blood. Conclusions:The mean flow velocity in the middle cerebral artery, as a parameter of cerebral blood flow, was low during mild hypothermia, whereas cerebral oxygen extraction remained normal, suggesting decreased cerebral metabolic activity. We demonstrated that CO2 reactivity is preserved during hypothermia in these patients.

Rewarming after hypothermia after cardiac arrest shifts the inflammatory balance.

Objectives:The aim of this study was to simultaneously analyze the key components of the cerebral and systemic inflammatory response over time in cardiac arrest patients during mild therapeutic hypothermia and rewarming. Design and Setting:Clinical observational study in a tertiary care university hospital. Patients:Ten comatose patients after out-of-hospital cardiac arrest. Interventions:All patients were cooled to 32–34°C for 24 hrs. After 24 hrs patients were passively rewarmed to normothermia. Measurements and Main Results:On admission and at 3, 6, 12, 24, and 48 hrs blood samples were taken from the arterial and jugular bulb catheter. Proinflammatory and anti-inflammatory cytokines and chemokines (interleukin-1ra, interleukin-1&;, interleukin-6, interleukin-8, interleukin-10, interleukin-18, monocyte chemotactic protein-1, high-mobility group box-1 and tumor necrosis factor-&agr;), complement activation products (C4d, Bb, C3a, and terminal complement complex), and the adhesion molecule soluble intercellular adhesion molecule were measured. Mean temperatures at the start of the study and at 12 and 24 hrs were 33.7 ± 0.9°C, 32.7 ± 0.92°C, and 34.5 ± 1.5°C, respectively. Passive rewarming resulted in a temperature of 37.8 ± 0.5°C at 48 hrs. The proinflammatory cytokine interleukin-6 increased from 12 to 24 hrs and returned to baseline levels after 48 hrs. In contrast, the chemokines interleukin-8 and monocyte chemotactic protein-1 stayed relatively high from the start and during the hypothermia period, decreasing to baseline levels after 48 hrs. The anti-inflammatory cytokines interleukin-10 and interleukin-1ra did not significantly change during mild therapeutic hypothermia and rewarming, although low values of interleukin-10 were observed after rewarming. A significant increase after rewarming was demonstrated on high-mobility group box-1 concentrations in the jugular bulb, whereas soluble intercellular adhesion molecule increased significantly during hypothermia and remained at this level after rewarming. Complement activation was increased on admission and decreased after induction of hypothermia, followed by a secondary increase during rewarming. No significant differences between any of the biomarkers were found between samples from the arterial and jugular bulb catheter. Conclusions:Complement activation occurs during rewarming from mild therapeutic hypothermia after cardiac arrest. Interleukin-6 increased already from 12 to 24 hrs, concomitantly with a significant increase in the temperature seen during this period of mild therapeutic hypothermia. The optimal rate of rewarming is unknown. Additional clinical studies are needed to determine the optimal rewarming rate and strategy. (Crit Care Med 2012; 40:–1142)

On-line blood viscosity monitoring in vivo with a central venous catheter, using electrical impedance technique.

Blood viscosity is an important determinant of microvascular hemodynamics and also reflects systemic inflammation. Viscosity of blood strongly depends on the shear rate and can be characterized by a two parameter power-law model. Other major determinants of blood viscosity are hematocrit, level of inflammatory proteins and temperature. In-vitro studies have shown that these major parameters are related to the electrical impedance of blood. A special central venous catheter was developed to measure electrical impedance of blood in-vivo in the right atrium. Considering that blood viscosity plays an important role in cerebral blood flow, we investigated the feasibility to monitor blood viscosity by electrical bioimpedance in 10 patients during the first 3 days after successful resuscitation from a cardiac arrest. The blood viscosity-shear rate relationship was obtained from arterial blood samples analyzed using a standard viscosity meter. Non-linear regression analysis resulted in the following equation to estimate in-vivo blood viscosity (Viscosity(imp)) from plasma resistance (R(p)), intracellular resistance (R(i)) and blood temperature (T) as obtained from right atrium impedance measurements: Viscosity(imp)=(-15.574+15.576R(p)T)SR ((-.138RpT-.290Ri)). This model explains 89.2% (R(2)=.892) of the blood viscosity-shear rate relationship. The explained variance was similar for the non-linear regression model estimating blood viscosity from its major determinants hematocrit and the level of fibrinogen and C-reactive protein (R(2)=.884). Bland-Altman analysis showed a bias between the in-vitro viscosity measurement and the in-vivo impedance model of .04 mPa s at a shear rate of 5.5s(-1) with limits of agreement between -1.69 mPa s and 1.78 mPa s. In conclusion, this study demonstrates the proof of principle to monitor blood viscosity continuously in the human right atrium by a dedicated central venous catheter equipped with an impedance measuring device. No safety problems occurred and there was good agreement with in-vitro measurements of blood viscosity.

Effects of prolonged mild hypothermia on cerebral blood flow after cardiac arrest.

Objective: The aim of the present study was to assess the cerebral blood flow and cerebral oxygen extraction in adult patients after pulseless electrical activity/asystole or resistant ventricular fibrillation who were treated with mild therapeutic hypothermia for 72 hrs. Design: Observational study. Setting: Tertiary care university hospital. Patients: Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation. Intervention: Treatment with mild therapeutic hypothermia for 72 hrs. Measurements and Main Results: Mean flow velocity in the middle cerebral artery was measured by transcranial Doppler at 12, 24, 36, 48, 60, 72, 84, 96, and 108 hrs after admission. Jugular bulb oxygenation was measured at the same intervals. Mean flow velocity in the middle cerebral artery was low (26.5 (18.7–48.0) cm/sec) at admission and significantly increased to 63.9 (45.6–65.6) cm/sec at 72 hrs (p = .002). Upon rewarming, the mean flow velocity in the middle cerebral artery remained relatively constant with a mean flow velocity in the middle cerebral artery of 71.5 (56.0–78.5) at 108 hrs (p = .381). Jugular bulb oxygenation at the start of the study was 57.0 (51.0–61.3)% and gradually increased to 81.0 (78.5–88.0)% at 72 hrs (p = .003). Upon rewarming, the jugular bulb oxygenation remained constant with a jugular bulb oxygenation of 84.0 (77.3–86.3)% at 108 hrs (p = .919). There were no differences in mean flow velocity in the middle cerebral artery, pulsatility index, and jugular bulb oxygenation between survivors and nonsurvivors. Conclusions: Temperature by itself is probably not a major determinant in regulation of cerebral blood flow after cardiac arrest. The relatively low mean flow velocity in the middle cerebral artery in combination with normal jugular bulb oxygenation values suggests a reduction in cerebral metabolic activity that may contribute to the neuroprotective effect of (prolonged) mild therapeutic hypothermia in the delayed hypoperfusion phase.

Hypothermia does not increase the risk of infection: a case control study

IntroductionHypothermia may improve outcome in patients after traumatic brain injury, especially when hypothermia is maintained for more than 48 hours. In the acute phase, patients with severe brain injury are more vulnerable to infections. Prolonged hypothermic treatment may further enhance the risk of infection. Selective decontamination of the digestive tract (SDD) reduces the risk of respiratory tract infections. The aim of this study was to investigate the incidence of infections in patients treated with hypothermia and normothermia while receiving SDD.MethodsIn this retrospective case control study 35 patients treated with prolonged hypothermia (cases) were identified and 169 patients with severe brain injury were included (controls). Propensity score matching was performed to correct for differences in baseline characteristics and clinical parameters. Primary outcome was the incidence of infection. The secondary endpoints were the micro-organisms found in the surveillance cultures and infection. In addition, a number of clinical characteristics were assessed.ResultsThe demographic and clinical data indicated that the cases and controls were well matched. The overall risk of infection during ICU stay was 20% in the hypothermia groups versus 34.4% in the normothermia group (P = 0.388). Pneumonia was diagnosed in 11.4% of patients in both groups (P = 1.000). The incidence of meningitis, wound infection, bacteremia, and urinary tract infection was low and comparable between the groups. SDD surveillance cultures indicated a higher colonization with gram-negative bacteria in the rectal samples of the hypothermia patients.ConclusionsHypothermia does not increase the risk of infection in patients treated with SDD.

Effects of viscosity on cerebral blood flow after cardiac arrest.

Objectives:To determine blood viscosity in adult comatose patients treated with mild therapeutic hypothermia after cardiac arrest and to assess the relation between blood viscosity, cerebral blood flow, and cerebral oxygen extraction. Design:Observational study. Setting:Tertiary care university hospital. Patients:Ten comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest. Intervention:Treatment with mild therapeutic hypothermia for 24 hours followed by passive rewarming to normothermia. Measurements and Main Results:Median viscosity at shear rate 50/s was 5.27 mPa · s (4.29–5.91 mPa · s) at admission; it remained relatively stable during the first 12 hours and decreased significantly to 3.00 mPa · s (2.72–3.58 mPa · s) at 72 hours (p < 0.001). Median mean flow velocity in the middle cerebral artery was low (27.0 cm/s [23.8–30.5 cm/s]) at admission and significantly increased to 63.0 cm/s (51.0–80.0 cm/s) at 72 hours. Median jugular bulb saturation at the start of the study was 61.5% (55.5–75.3%) and significantly increased to 73.0% (69.0–81.0%) at 72 hours. Median hematocrit was 0.41 L/L (0.36–0.44 L/L) at admission and subsequently decreased significantly to 0.32 L/L (0.27–0.35 L/L) at 72 hours. Median C-reactive protein concentration was low at admission (2.5 mg/L [2.5–6.5 mg/L]) and increased to 101 mg/L (65–113.3 mg/L) in the following hours. Median fibrinogen concentration was increased at admission 2,795 mg/L (2,503–3,565 mg/L) and subsequently further increased to 6,195 mg/L (5,843–7,368 mg/L) at 72 hours. There was a significant negative association between blood viscosity and the mean flow velocity in the middle cerebral artery (p = 0.0008). Conclusions:Changes in blood viscosity in vivo are associated with changes in flow velocity in the middle cerebral artery. High viscosity early after cardiac arrest may reduce cerebral blood flow and may contribute to secondary brain injury. Further studies are needed to determine the optimal viscosity during the different stages of the postcardiac arrest syndrome.