Danica Krizanac

Rapid induction of therapeutic hypothermia using convective-immersion surface cooling: Safety, efficacy and outcomes

Therapeutic hypothermia has become an accepted part of post-resuscitation care. Efforts to shorten the time from return of spontaneous circulation to target temperature have led to the exploration of different cooling techniques. Convective-immersion uses a continuous shower of 2 degrees C water to rapidly induce hypothermia. The primary purpose of this multi-center trial was to evaluate the feasibility and speed of convective-immersion cooling in the clinical environment. The secondary goal was to examine the impact of rapid hypothermia induction on patient outcome. 24 post-cardiac arrest patients from 3 centers were enrolled in the study; 22 agreed to participate until the 6-month evaluations were completed. The median rate of cooling was 3.0 degrees C/h. Cooling times were shorter than reported in previous studies. The median time to cool the patients to target temperature (<34 degrees C) was 37 min (range 14-81 min); and only 27 min in a subset of patients sedated with propofol. Survival was excellent, with 68% surviving to 6 months; 87% of survivors were living independently at 6 months. Conductive-immersion surface cooling using the ThermoSuit System is a rapid, effective method of inducing therapeutic hypothermia. Although the study was not designed to demonstrate impact on outcomes, survival and neurologic function were superior to those previously reported, suggesting comparative studies should be undertaken. Shortening the delay from return of spontaneous circulation to hypothermic target temperature may significantly improve survival and neurologic outcome and warrants further study.

Non-invasive continuous cerebral temperature monitoring in patients treated with mild therapeutic hypothermia: an observational pilot study.

AIM OF THE STUDY To investigate if body temperature as measured with a prototype of a non-invasive continuous cerebral temperature sensor using the zero-heat-flow method to reflect the oesophageal temperature (core temperature) during mild therapeutic hypothermia after cardiac arrest. METHODS In patients over 18 years old with restoration of spontaneous circulation after cardiac arrest, a temperature sensor that uses the zero-heat-flow principle was placed on the forehead during the periods of cooling and re-warming. This temperature was compared to oesophageal temperature as the primary temperature-monitoring site. To assess agreement, we used the Bland-Altman approach and Lins concordance correlation coefficient. RESULTS From September 2008 to April 2009, data from 19 patients were analysed. The median time from restoration of spontaneous circulation until temperature sensor application was 53min (interquartile range, 31; 96). All sensors were removed when a core temperature of 36 degrees C was reached. These measurements were in agreement with oesophageal temperature measurements. No allergic reaction, rash or other irritation occurred on the skin around or under the probes. Bland-Altman results showed a bias of -0.12 degrees C and 95% limits of agreement of -0.59 and +0.36 degrees C. Lins concordance correlation coefficient was 0.98. CONCLUSIONS Body temperature measurements using a non-invasive continuous cerebral temperature sensor prototype that uses the zero-heat-flow method accurately reflected oesophageal temperature measurements during mild therapeutic hypothermia in patients with restoration of spontaneous circulation after cardiac arrest.

Cardiac arrest survivors with moderate elevated body mass index may have a better neurological outcome: A cohort study

AIM Body mass index (BMI) may influence the quality of cardiopulmonary resuscitation and may influence prognosis after cardiac arrest. To review the direct effect of obesity on outcome after cardiac arrest, the following cohort study was conducted. METHODS This study based on a cardiac arrest registry comprising all adult patients with cardiac arrest of non-traumatic origin and restoration of spontaneous circulation (ROSC) admitted to the department of emergency medicine of a tertiary-care facility. Data were collected between January 1992 and December 2007 according to the Utstein criteria. We assessed the association between BMI according to the WHO classification (underweight, BMI<18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese ≥ 30), six-month survival and neurological recovery. RESULTS Analysis was carried out on a total of 1915 adult patients (32% female). Patients had a median age of 59 years (interquartile range [IQR] 49-70) and a median BMI of 26.0 (IQR 23.9-29.1). Survival to six months was 50%. There was no significant difference in survival between the BMI groups (underweight 46%, normal weight 47%, overweight 52%, obese 51%). In a multivariate analysis neurological outcome was better in overweight patients as compared to subjects with normal BMI (odds ratio 1.35; 95% confidence interval 1.02-1.79). CONCLUSION Body mass index may have no direct influence on six-month survival after cardiac arrest, but patients with moderately elevated BMI may have a better neurological prognosis.

Femoro-iliacal artery versus pulmonary artery core temperature measurement during therapeutic hypothermia: An observational study

AIM OF THE STUDY Therapeutic hypothermia after cardiac arrest improves neurologic outcome. The temperature measured in the pulmonary artery is considered to best reflect core temperature, yet is limited by invasiveness. Recently a femoro-arterial thermodilution catheter (PiCCO-Pulse Contour Cardiac Output) has been introduced in clinical practice as a safe and accurate haemodynamic monitoring system, which is also able to measure blood temperature. The aim of the study was to investigate, if the temperature measured with the PiCCO catheter reflects pulmonary artery temperature better than other sites during therapeutic hypothermia. METHODS In this observational study twenty patients after cardiac arrest and successful resuscitation were cooled with various cooling methods to 33 ± 1°C for 24h, followed by rewarming. Temperatures were recorded continuously in the pulmonary artery (Tpa), femoro-iliacal artery (Tpicco), ear canal (Tear), oesophagus (Toeso) and urinary bladder (Tbla). We assessed agreement of methods using the Bland Altman approach including bias and limits of agreement (LA). RESULTS All other sites differed significantly from Tpa with the bias varying from 0.4°C (Tbla) to -0.6°C (Tear). Standard deviations varied from 0.1°C (Tpicco, Toeso) to 0.5°C (Tear). For all sites bias was closer to zero with increasing average temperatures. Bias tended to be larger in the cooling phase compared to overall measurements. CONCLUSIONS Temperature measurement in the femoro-iliacal artery (Tpicco) reflects the gold standard of pulmonary artery temperature most accurately, especially during the cooling phase. Tpicco is easily accessible and might be used for monitoring core temperature without the need for additional temperature probes.

Changes in interleukin-10 mRNA expression are predictive for 9-day survival of pigs in an emergency preservation and resuscitation model

AIM OF THE STUDY This study aimed at evaluating (I) the impact of different intra-arrest hypothermia levels on the expression of selected cytokines and (II) their prognostic value for 9-day survival. METHODS Female Large White pigs (n=21, 31-38 kg) were subjected to 15 min of ventricular fibrillation, followed by intra-arrest cardiopulmonary bypass cooling for 1, 3, or 5 min achieving brain temperatures (Tbr) of 30.4+/-1.6, 24.2+/-4.6 and 18.8+/-4.0 degrees C. After 40 min of controlled rewarming, pigs were defibrillated and kept at Tbr of 34.5 degrees C for 20 h, survival was for 9 days. Plasma samples were analysed for interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-10 levels by ELISA. Total RNA out of peripheral blood mononuclear cells was analysed by real-time PCR for IL-1, IL-2, IL-4, IL-10, TNF-alpha, interferon-gamma, inducible NO synthase, and heme oxygenase-1 gene expressions. RESULTS Plasma IL-6 and TNF-alpha levels significantly (p=0.0001 and 0.0003) increased in all animals within 1h after resuscitation with no significant differences between groups. Pigs surviving exhibited a decrease in IL-10 expression between baseline and intra-arrest values as compared to non-surviving animals, which showed a slight increase (p=0.0078). ROC curve analysis revealed that changes in IL-10 expression had a good prognostic power for survival to day 9 (area under the curve=0.882). CONCLUSION The systemic inflammatory response syndrome after cardiac arrest was reflected by a remarkable increase of plasma IL-6 and TNF-alpha levels. Intra-arrest hypothermia levels did not influence the expression of selected cytokines. As prognostic marker for survival IL-10 was identified with decreasing mRNA levels during cardiac arrest in survivors.

Temperature monitored on the cuff surface of an endotracheal tube reflects body temperature

Objective:When treating patients with cardiac arrest with mild therapeutic hypothermia, a reliable and easy-to-use temperature probe is desirable. This study was conducted to investigate the accuracy and safety of tracheal temperature as a measurement of body temperature. Design:Observational cohort study. Setting:Emergency department of a tertiary care university hospital. Patients:Patients successfully resuscitated from cardiac arrest intended for mild hypothermia therapy. Interventions:Intubation was performed with a newly developed endotracheal tube that contains a temperature sensor inside the cuff surface. During the cooling, mild hypothermia maintenance, and rewarming phases, the temperature was recorded minute by minute. These data were compared with the temperature assessed by esophageal and blood temperature probes. Thereafter, tracheoscopy was performed to evaluate the condition of the tracheal mucosa. Measurements and Main Results:Approximately 2000 measurements per temperature sensor per patient were recorded in 21 patients. The mean bias between the blood temperature and the tracheal temperature was −0.16°C (limits of agreement: −0.36°C to 0.04°C). The mean bias between the esophageal and tracheal temperatures was −0.22°C (limits of agreement: −0.49°C to 0.07°C). Agreement between temperature probes investigated by the Bland-Altman method showed a mean bias of less than −¼°C, and time lags assessed graphically by hysteresis plots were negligible. No clinically relevant injury to the tracheal mucosa was detected. Conclusion:Temperature monitoring at the cuff surface of an endotracheal tube is safe and provides accurate and reliable data in all phases of therapeutically induced mild hypothermia after cardiac arrest.

Outcome after resuscitation using controlled rapid extracorporeal cooling to a brain temperature of 30 ◦ C, 24 ◦ C and 18 ◦ C during cardiac arrest in pigs ,

AIM OF THE STUDY To identify the optimal level of hypothermia during cardiac arrest, just prior to resuscitation with an extracorporeal cooling system and without fluid overload, for neurological outcome at day 9 in pigs. METHODS In a prospective randomised laboratory investigation, 24 female Large White pigs (31-38 kg) underwent ventricular-fibrillation cardiac arrest for 15 min, followed by 1 min, 3 min or 5 min (n=8 per group) of 4 degrees C cooling with an extracorporeal cooling system via an aortic balloon catheter and resuscitation with cardiopulmonary bypass. Sixty minutes following induction of cardiac arrest, defibrillation attempts were started. Mild hypothermia (34.5 degrees C) and intensive care were continued for 20 h and final outcome was evaluated after 9 days. RESULTS Brain temperature decreased from 38.5 degrees C to 30.4+/-1.6 degrees C within 221+/-81 s in the 1-min group; to 24.2+/-4.6 degrees C within 375+/-127 s in the 3-min group; and to 18.8+/-4.0 degrees C within 450+/-121 s in the 5-min group. Restoration of spontaneous circulation was achieved in seven (1-min group), six (3-min group) and six (5-min group) animals (p=0.78), whereas survival to 9 days was only achieved in six, three and three animals in each group (p=0.22), respectively. CONCLUSIONS An extracorporeal cooling system rapidly induced brain hypothermia following prolonged normovolaemic cardiac arrest in pigs. Difference in outcome was not statistically significant amongst the three groups with various levels of hypothermia (30 degrees C, 24 degrees C and 18 degrees C) during cardiac arrest prior to resuscitation; however, the animals with the least temperature reduction showed a trend to better survival at 9 days. Further studies are necessary to investigate optimised methods for induction, as well as level, of cerebral hypothermia.

Seasonal variability and influence of outdoor temperature on body temperature of cardiac arrest victims

AIM OF THE STUDY Mild therapeutic hypothermia is a major advance in post-resuscitation-care. Some questions remain unclear regarding the time to initiate cooling and the time to achieve target temperature below 34 °C. We examined whether seasonal variability of outside temperature influences the body temperature of cardiac arrest victims, and if this might have an effect on outcome. METHODS Patients with witnessed out-of-hospital cardiac arrests were enrolled retrospectively. Temperature variables from 4 climatic stations in Vienna were provided from the Central Institute for Meteorology and Geodynamics. Depending on the outside temperature at the scene the study participants were assigned to a seasonal group. To compare the seasonal groups a Students t-test or Mann-Whitney U test was performed as appropriate. RESULTS Of 134 patients, 61 suffered their cardiac arrest during winter, with an outside temperature below 10 °C; in 39 patients the event occurred during summer, with an outside temperature above 20 °C. Comparing the tympanic temperature recorded at hospital admission, the median of 36 °C (IQR 35.3-36.3) during summer differed significantly to winter with a median of 34.9 °C (IQR 34-35.6) (p<0.05). This seasonal alterations in core body temperature had no impact on the time-to-target-temperature, survival rate or neurologic recovery. CONCLUSION The seasonal variability of outside temperature influences body temperature of out-of-hospital cardiac arrest victims.

Rapid induction of hypothermia with a small volume aortic flush during cardiac arrest in pigs

PURPOSE The induction of deep cerebral hypothermia (15°C) via large-volume cold (4°C) saline aortic flush during cardiac arrest and resuscitation with cardiopulmonary bypass improves neurologic outcome in pigs. We hypothesized that induction of mild cerebral hypothermia (33°C) via smaller volume and resuscitation without bypass will improve survival and neurologic outcome after 15 minutes of cardiac arrest as compared with conventional resuscitation attempts. BASIC PROCEDURES Twenty-four pigs (29-38 kg) underwent ventricular fibrillation cardiac arrest for 15 minutes. Conventional resuscitation (n=8) was compared with hypothermic (4°C, n=8) and normothermic (38.5°C, n=8) aortic flush (30 mL/kg) at the beginning of resuscitation efforts, with defibrillation attempts 2 minutes later. Outcomes after 9 days were compared. MAIN FINDINGS In the hypothermic flush group, brain temperature decreased from 38.3°C±0.5°C to 33°C±0.5°C within 277±112 seconds. We observed considerably higher mean coronary perfusion pressures in the normothermic and hypothermic flush groups (hypothermic vs conventional, P=.023; normothermic vs conventional, P=.041). Three animals of each flush group, compared with none of the conventional group, achieved restoration of spontaneous circulation (P=.2); and 3 pigs of the hypothermic flush group and 2 pigs of the normothermic flush group survived to 9 days without differences in neurologic outcome. PRINCIPAL CONCLUSION A smaller volume, cold saline aortic flush during prolonged cardiac arrest rapidly induces mild cerebral hypothermia to 33°C and improves coronary perfusion pressure but does not result in a significant improvement in outcome as compared with conventional resuscitation attempts.

Comparison of surface cooling and invasive cooling for rapid induction of mild therapeutic hypothermia in pigs—Effectiveness of two different devices ,

AIM OF THE STUDY The effectiveness and safety of non-invasive surface cooling was compared to invasive endovascular cooling in an animal model. METHODS Eight healthy pigs (29-38 kg) were cooled twice, starting in the first 4 pigs with unique surface cooling pads followed by endovascular cooling. In the second 4 pigs the order was reversed. The goal was to quickly lower pulmonary artery temperature from 38 to 33°C. A paired t-test was used to compare cooling rates (°C/h, mean±standard deviation) between both cooling techniques. RESULTS Mean non-invasive surface cooling rate (11.9±3.8°C/h) significantly exceeded mean invasive cooling rate (3.9±0.7°C/h; p<0.001). The mean difference in cooling rates was 8.0±3.6°C/h. No surface cooling related adverse skin reactions were observed. CONCLUSIONS Surface cooling is a simple method for achieving fast cooling rates. In our animal model, non-invasive cooling was three times faster than rapid endovascular cooling without overshoot.