Effects of levemopamil on neurologic and histologic outcome after cardiac arrest in cats.

BACKGROUND AND METHODS: A study was performed to examine the effects of the calcium-channel blocker levemopamil on neurologic outcome and neuropathology in a clinically relevant model of complete global cerebral ischemia (ventricular fibrillation in cats). Levemopamil was administered to cats starting 5 mins after resuscitation from 14 mins of cardiac arrest. In a "blinded" manner, 46 animals received levemopamil 1 mg/kg over 15 mins followed by 10 micrograms/kg.min for 16 hrs or vehicle. In a nonblinded manner, eight additional animals were pretreated with levemopamil beginning 45 mins before cardiac arrest. After resuscitation, levemopamil was infused at 10 micrograms/kg.min for 16 hrs. Animals in all three groups remained sedated, paralyzed, and mechanically ventilated for 24 to 30 hrs after resuscitation. Neurologic examinations were performed at 2, 4, and 7 days after resuscitation. Thirty-five cats were entered into data analysis (16 levemopamil posttreated, 14 vehicle-treated, and 5 levemopamil pretreated). RESULTS: Neurologic deficit scores and over-all neuropathologic scores did not differ among groups at any interval after resuscitation. However, the occipital cortex and CA1 region of the pretreated animals showed less severe damage than was observed in the animals that received levemopamil or vehicle, starting after resuscitation (p less than .01). CONCLUSIONS: Postarrest administration of levemopamil was not associated with improved neurologic or neuropathologic outcome. However, the data suggest that prearrest administration may result in regionally selective improvement in neuropathology.     

Long-term neurological outcome after cardiac arrest and therapeutic hypothermia

Aim of the studyTo analyse the neurological status of survivors after cardiac arrest (CA) treated with hypothermia.MethodsWe prospectively included all patients with CA treated with hypothermia at intensive care units (ICU) in two university hospitals and one regional hospital. All adult survivors at 6 months after CA, n = 48, were invited for neurological follow-up and 43 accepted. History, clinical status, ability testing and questionnaires were administered to screen for difficulties, including Assessment of Motor and Process Skills, Neurobehavioral Cognitive Status Examination, Frontal Lobe Assessment Battery, EQ-VAS quality of life scale, Skåne Sleep Index, Hospital Anxiety and Depression Rating Scale, Self-reported Montgomery and Åstrand Depression Rating Scale, Global Deterioration Scale, Rivermead Behavioural Memory Test, and the Cerebral Performance Categories (CPC).ResultsNo patient was found to be in a chronic vegetative state and all patients were living at home, one with extensive help. Thirty-six patients were in CPC1 at follow-up, and some degree of neurological sequelae was found in 40 patients, but was mild in all but 3. Three patients had no subjective complaints, nor could any deficits be detected. Initial defects improved over-time. Short-term memory loss, executive frontal lobe dysfunction along with mild depression and sleep rhythm disturbances were the most common findings.ConclusionsMild cognitive impairment is common following hypothermia-treated cardiac arrest but has little effect on activities of daily living or quality of life.     

The influence of rewarming after therapeutic hypothermia on outcome after cardiac arrest

IntroductionTreatment with hypothermia has been shown to improve outcome after cardiac arrest (CA). Current consensus is to rewarm at 0.25–0.5 °C/h and avoid fever. The aim of this study was to investigate whether active rewarming, the rate of rewarming or development of fever after treatment with hypothermia after CA was correlated with poor outcome.MethodsThis retrospective cohort study included adult patients treated with hypothermia after CA and admitted to the intensive care unit between January 2006 and January 2009. The average rewarming rate from end of hypothermia treatment (passive rewarming) or start active rewarming until 36 °C was dichotomized in a high (≥0.5 °C/h) or normal rate (<0.5 °C/h). Fever was defined as > 38 °C within 72 h after admission. Poor outcome was defined as death, vegetative state, or severe disability after 6 months.ResultsFrom 128 included patients, 56% had a poor outcome. Actively rewarmed patients (38%) had a higher risk for poor outcome, OR 2.14 (1.01–4.57), p < 0.05. However, this effect disappeared after adjustment for the confounders age and initial rhythm, OR 1.51 (0.64–3.58). A poor outcome was found in 15/21 patients (71%) with a high rewarming rate, compared to 54/103 patients (52%) with a normal rewarming rate, OR 2.61 (0.88–7.73), p = 0.08. Fever was not associated with outcome, OR 0.64 (0.31–1.30), p = 0.22.ConclusionsThis study showed that patients who needed active rewarming after therapeutic hypothermia after CA did not have a higher risk for a poor outcome. In addition, neither speed of rewarming, nor development of fever had an effect on outcome.     

Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia

Objective

Therapeutic temperature modulation is recommended after cardiac arrest (CA). However, body temperature (BT) regulation has not been extensively studied in this setting. We investigated BT variation in CA patients treated with therapeutic hypothermia (TH) and analyzed its impact on outcome.

Methods

A prospective cohort of comatose CA patients treated with TH (32–34 °C, 24 h) at the medical/surgical intensive care unit of the Lausanne University Hospital was studied. Spontaneous BT was recorded on hospital admission. The following variables were measured during and after TH: time to target temperature (TTT = time from hospital admission to induced BT target <34 °C), cooling rate (spontaneous BT − induced BT target/TTT) and time of passive rewarming to normothermia. Associations of spontaneous and induced BT with in-hospital mortality were examined.

Results

A total of 177 patients (median age 61 years; median time to ROSC 25 min) were studied. Non-survivors (N = 90, 51%) had lower spontaneous admission BT than survivors (median 34.5 [interquartile range 33.7–35.9] °C vs. 35.1 [34.4–35.8] °C, p = 0.04). Accordingly, time to target temperature was shorter among non-survivors (200 [25–363] min vs. 270 [158–375] min, p = 0.03); however, when adjusting for admission BT, cooling rates were comparable between the two outcome groups (0.4 [0.2–0.5] °C/h vs. 0.3 [0.2–0.4] °C/h, p = 0.65). Longer duration of passive rewarming (600 [464–744] min vs. 479 [360–600] min, p < 0.001) was associated with mortality.

Conclusions

Lower spontaneous admission BT and longer time of passive rewarming were associated with in-hospital mortality after CA and TH. Impaired thermoregulation may be an important physiologic determinant of post-resuscitation disease and CA prognosis. When assessing the benefit of early cooling on outcome, future trials should adjust for patient admission temperature and use the cooling rate rather than the time to target temperature.     

Low-dose nitroglycerine improves outcome after cardiac arrest in rats

Objective

The aim of this study was to evaluate the outcome of intravenously applied nitroglycerine (NTG, 1 μg kg⁻¹ min⁻¹ for 1 h) after resuscitation from an asphyxia cardiac arrest (ACA) insult. We hypothesized that NTG infused for 1 h after the return of spontaneous circulation (ROSC) would improve functional and neuro-morphological outcomes.

Methods

Adult rats were subjected to 8 min of ACA followed by resuscitation. There were three treatment groups: ACA, ACA + NTG and sham operated. Vital and blood parameters were monitored during the 1 h post-resuscitation intensive care phase. After survival times of 3, 6, 12, 24, 72 h and 7 days, the neurological deficit score (NDS) was measured. Histological evaluation of the hippocampus, cortex, the thalamic reticular nucleus and the caudate-putamen was performed 7 days post insult.

Results

We found that NTG (i) induced significantly higher initial MAP peaks; (ii) resulted in a less-pronounced elevation of heart rates after ROSC with significantly faster normalization to baseline levels; and (iii) influenced glucose metabolism, temporarily elevating blood glucose to non-physiological levels. Even so, NTG (iv) improved the neurological outcome and (v) reduced neurodegeneration, mainly in the hippocampal CA1 region. A significant NTG-associated decrease in blood pressure did not occur.

Conclusion

The effect of low-dosed NTG applied post-resuscitation appears to be neuroprotective, demonstrated by reduced hippocampal damage and a better NDS, even with temporarily elevated blood glucose to non-physiological levels. Thus, additional studies are needed to evaluate NTG-triggered mechanisms and optimized dosages before clinical translation should be considered.Animal study institutional protocol number: 42502-2-2-947-Uni-MD.     

Optimal management of shivering during therapeutic hypothermia after cardiac arrest

Both pharmacological and nonpharmacological methods are used to control shivering in therapeutic hypothermia. An evidence-based protocol based on the most current research has been developed for the management of shivering during therapeutic hypothermia. Meperidine is the drug of choice and provides the greatest reduction in the shivering threshold. Other effective pharmacological agents recommended for reducing the threshold include dexmedetomidine, midazolam, fentanyl, and magnesium sulfate. In addition, skin counterwarming techniques, such as use of an air-circulating blanket, are effective nonpharmacological methods for reducing shivering when used in conjunction with medication. As a last resort, neuromuscular blocking agents are considered appropriate therapy for management of refractory shivering.     

The association between hemoglobin concentration and neurologic outcome after cardiac arrest

PurposeThe purpose of the study is to determine the association between hemoglobin concentration (Hgb) and neurologic outcome in postarrest patients.MethodsWe conducted a retrospective cohort study using the Penn Alliance for Therapeutic Hypothermia (PATH) cardiac arrest registry. Inclusion criteria were resuscitated cardiac arrest (inhospital or out of hospital) and an Hgb value recorded within 24 hours of return of spontaneous circulation. The primary outcome was favorable neurologic status at hospital discharge. Survival to hospital discharge was a secondary outcome.ResultsThere were 598 eligible patients from 21 hospitals. Patients with favorable neurologic outcome had significantly higher median Hgb in the first 2 hours (12.7 vs 10.5 g/dL; P < .001) and 6 hours (12.6 vs 10.6 g/dL; P < .001) postarrest. Controlling for age, pulseless rhythm, etiology, location of arrest, receipt of targeted temperature management, hematologic or metastatic malignancy, or preexisting renal insufficiency, there was a significant relationship between Hgb and neurologic outcome within the first 6 hours after arrest (odds ratio, 1.23; 95% confidence interval, 1.09-1.38) and survival to hospital discharge (odds ratio, 1.20; 95% confidence interval, 1.08-1.34).ConclusionHigher Hgb after cardiac arrest is associated with favorable neurologic outcome, particularly within the first 6 hours. It is unclear if this effect is due to impaired oxygen delivery or if Hgb is a marker for more severe illness.     

Amplitude-integrated EEG (aEEG) predicts outcome after cardiac arrest and induced hypothermia

Objective To evaluate the use of continuous amplitude-integrated EEG (aEEG) as a prognostic tool for survival and neurological outcome in cardiac arrest patients treated with hypothermia.Design Prospective, observational study.Setting Multidisciplinary intensive care unit in a university hospital.Intervention Comatose survivors of cardiac arrest were treated with induced hypothermia for 24 h. An aEEG recording was initiated upon arrival at the ICU and continued until the patient regained consciousness or, if the patient remained in coma, no longer than 120 h. The aEEG recording was not available to the ICU physician, and the aEEG tracings were interpreted by a neurophysiologist with no knowledge of the patient's clinical status. Only clinically visible seizures were treated. Measurements and results Thirty-four consecutive hypothermia-treated cardiac arrest survivors were included. At normothermia (mean 37 h after cardiac arrest), the aEEG pattern was discriminative for outcome. All 20 patients with a continuous aEEG at this time regained consciousness, whereas 14 patients with pathological aEEG patterns (flat, suppression-burst or status epilepticus) did not regain consciousness and died in hospital. Patients were evaluated neurologically upon discharge from the ICU and after 6 months, using the Cerebral Performance Category (CPC) scale. Eighteen patients were alive with a good cerebral outcome (CPC 1--2) at 6-month follow-up. Conclusion A continuous aEEG pattern at the time of normothermia was discriminative for regaining consciousness. aEEG is an easily applied method in the ICU setting.     

Mild protective and resuscitative hypothermia for asphyxial cardiac arrest in rats

It has been shown in dogs that mild hypothermia (34°C) during or immediately after ventricular fibrillation cardiac arrest can improve cerebral outcome. The effect of mild hypothermia on outcome after 8 minutes of asphyxiation (5 minutes' cardiac arrest) was studied for the first time in rats. Restoration of spontaneous circulation was with external cardiopulmonary resuscitation and observation to 72 hours. Three groups of 10 rats each were studied. At 72 hours postarrest, compared with the normothermic control group 1, final overall performance categories (OPC) and neurological deficit scores (NDS) were numerically better in the resuscitative (post-arrest) hypothermia group 2 and significantly better in the protective (pre-intra-arrest) hypothermia group 3 (P < .05). Total brain histopathological damage scores (HDS) were 17 ± 5 in group 1, 14 ± 6 in group 2 (NS), and 6 ± 2 in group 3 (P < .001 versus group 1). HDS correlated with OPC (r = .6, P < .05) and NDS (r = .7, P < .05). Mild hypothermia improved cerebral outcome after asphyxial cardiac arrest in rats, more when induced before than after arrest. The model's insult is within the therapeutic window, which makes it also suitable for screening other cerebral resuscitation potentials.     

Improvement in the hospital organisation of CPR training and outcome after cardiac arrest in Sweden during a 10-year period

Aim

To describe (a) changes in the organisation of training in cardiopulmonary resuscitation (CPR) and the treatment of cardiac arrest in hospital in Sweden and (b) the clinical achievement, i.e. survival and cerebral function, among survivors after in-hospital cardiac arrest (IHCA) in Sweden.

Methods

Aspects of CPR training among health care providers (HCPs) and treatment of IHCA in Sweden were evaluated in 3 national surveys (1999, 2003 and 2008). Patients with IHCA are recorded in a National Register covering two thirds of Swedish hospitals.

Results

The proportion of hospitals with a CPR coordinator increased from 45% in 1999 to 93% in 2008. The majority of co-ordinators are nurses. The proportions of hospitals with local guidelines for acceptable delays from cardiac arrest to the start of CPR and defibrillation increased from 48% in 1999 to 88% in 2008. The proportion of hospitals using local defibrillation outside intensive care units prior to arrival of rescue team increased from 55% in 1999 to 86% in 2008.During the past 4 years in Sweden, survival to hospital discharge has been 29%. Among survivors, 93% have a cerebral performance category (CPC) score of I or II, indicating acceptable cerebral function.

Conclusion

During the last 10 years, there was a marked improvement in CPR training and treatment of IHCA in Sweden. During the past 4 years, survival after IHCA is high and the majority of survivors have acceptable cerebral function.     

Induced hyperthermia exacerbates neurologic neuronal histologic damage after asphyxial cardiac arrest in rats

BACKGROUND: Temperature is an important modulator of the evolution of ischemic brain injury--with hypothermia lessening and hyperthermia exacerbating damage. We recently reported that children resuscitated from predominantly asphyxial arrest often develop an initial spontaneous hypothermia followed by delayed hyperthermia. The initial hypothermia observed in these children was frequently treated with warming lights which, despite careful monitoring, often resulted in overshoot hyperthermia. We have previously reported in a rat model of asphyxial cardiac arrest that active warming, to prevent spontaneous hypothermia, worsens brain injury. OBJECTIVE: We sought to determine whether delayed induction of hyperthermia would worsen brain injury after asphyxial arrest in rats. DESIGN: Male Sprague-Dawley rats were asphyxiated for 8 mins and resuscitated. An implantable temperature probe was placed into the peritoneum before asphyxia. The probe is a component of a computer-based, radiofrequency, telemetry system (Minimitter, Sunriver, OR) that allowed continuous acquisition and manipulation (via heating and cooling devices) of core (intraperitoneal) body temperature. Body temperature was monitored but not manipulated for the first 24 hrs of recovery. Rats were assigned to: no temperature manipulation (n = 21), induced hyperthermia (40 +/- 0.5 degrees C) for 3 hrs beginning at 24 hrs (n = 21), or induced hyperthermia at 48 hrs (n = 10). Control groups included sham rats (all surgical procedures except asphyxia) treated with induced hyperthermia at 24 hrs (n = 4) or 48 hrs (n = 4) and na?ve rats (n = 4). Rats were killed at 7 days and injured neurons in hematoxylin and eosin stained coronal brain sections through dorsal hippocampus were scored in a semiquantitative manner on a scale of 0 to 10 (0 = normal; 1 = up to 10% neurons with ischemic neuronal changes; 10 = 90-100% neurons with ischemic neuronal changes). Normal-appearing neurons were also counted in CA1. The number of normal-appearing neurons in a 20x field in CA1 were also counted. MAIN RESULTS: All na?ve and sham hyperthermia control rats survived the protocol. There was a trend toward a larger mortality rate in asphyxiated rats treated with induced hyperthermia at 24 hrs (9 of 21 died) vs. asphyxiated rats without induced hyperthermia (3 of 21) or with hyperthermia induced at 48 hrs (3 of 10) (Kaplan-Meier p=.0595). Asphyxiated rats with hyperthermia induced at 24 hrs had larger (worse) histopathology damage scores than rats subjected to asphyxia without induced hyperthermia (9.3 +/- 1.5 vs. 6.2 +/- 2.6; p=.001). Histopathology damage scores in asphyxiated rats with hyperthermia induced at 48 hrs did not differ from those in rats asphyxiated without induced hyperthermia (6.4 +/- 3.0 vs. 6.2 +/- 2.6; p=.907). There were fewer normal-appearing CA1 neurons in asphyxiated rats with hyperthermia induced at 24 hrs vs. rats subjected to asphyxia without induced hyperthermia (33 +/- 13 vs. 67 +/- 36; p=.002). The number of normal-appearing CA1 neurons in asphyxiated rats with hyperthermia induced at 48 hrs did not differ from that in rats asphyxiated without induced hyperthermia (59 +/- 21 vs. 67 +/- 36; p=.885). CONCLUSIONS: Induced hyperthermia when administered at 24 hrs, but not 48 hrs, worsens ischemic brain injury in rats resuscitated from asphyxial cardiac arrest. This may have implications for postresuscitative management of children and adults resuscitated from cardiac arrest. The common clinical practice of actively warming patients with spontaneous hypothermia might result in iatrogenic injury if warming results in hyperthermic overshoot. Avoidance of hyperthermia induced by active warming at critical time periods after cardiac arrest may be important.     

The effect of mild hypothermia and induced hypertension on long term survival rate and neurological outcome after asphyxial cardiac arrest in rats

STUDY OBJECTIVE: we studied the long-term effect of a combined treatment with resuscitative mild hypothermia and induced hypertension on survival rate and neurological outcome after asphyxial cardiac arrest (CA) in rats. METHODS: 36 male Wistar rats, were randomised into three groups: Group I (n=10): anaesthetised with halothane and N(2)O/O(2) (70/30%) had vessel cannulation but no asphyxial CA; mechanical ventilation was continued to 1 h. Group II (n=13): under the same anaesthetic conditions and vessel cannulation, was subjected to asphyxial CA of 8 min, reversed by brief external heart massage and followed by mechanical ventilation to 1 h post restoration of spontaneous circulation (ROSC). Group III (n=13): received the same insult and resuscitation as described in group II, but in contrast to the previous group, a combination treatment of hypothermia (34 degrees C) and induced hypertension was started immediately after ROSC and maintained for 60 min ROSC. Survival rate and neurological deficit (ND) scores were determined before arrest, at 2 and 24 h, and each 24-h up to 4 weeks after ROSC. RESULTS: Baseline variables were the same in the three groups. Comparison of the asphyxial CA groups (groups II and III), showed an increased, although not statistically significant, survival rate at 72 h after ROSC in group III, and it became highly significant at 4 weeks after ROSC. The ND scores were the same in both asphyxial CA groups (groups II and III). CONCLUSIONS: Resuscitative mild hypothermia and induced hypertension after asphyxial CA in rats is associated with a better survival rate. This beneficial effect persisted for 4 weeks after ROSC.