Matti Pokela

IS MAINTAINED CRANIAL HYPOTHERMIA THE ONLY FACTOR LEADING TO IMPROVED OUTCOME AFTER RETROGRADE CEREBRAL PERFUSION? AN EXPERIMENTAL STUDY WITH A CHRONIC PORCINE MODEL

BACKGROUND Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect. METHODS Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals. RESULTS Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04). CONCLUSIONS These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.

The Role of Cerebral Microdialysis in Predicting the Outcome after Experimental Hypothermic Circulatory Arrest

Objective –To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. Design –Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20°C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. Results –Brain glucose concentrations were higher in animals that survived ( p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period ( p = 0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. Conclusion –Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.

Ph-stat versus alpha-stat perfusion strategy during experimental hypothermic circulatory arrest: a microdialysis study

BACKGROUND The superiority of the pH-stat to the alpha-stat acid-base strategy during cardiopulmonary bypass as a neuroprotective method during hypothermic circulatory arrest is still controversial. In the present study, brain metabolism and outcome have been evaluated in a surviving model of experimental hypothermic circulatory arrest. METHODS Twenty pigs undergoing 75-minutes of hypothermic circulatory arrest at a brain temperature of 18 degrees C were randomly assigned to the alpha-stat (n = 10) or pH-stat (n = 10) strategy during cardiopulmonary bypass. RESULTS The 7-day survival rate was 90% (9 of 10) in the pH-stat group and 10% (1 of 10) in the alpha-stat group. At the end of cooling, pH-stat strategy was associated with significantly lower brain lactate and pyruvate concentrations and brain lactate-glucose ratio. After reperfusion, brain concentrations of glycerol, lactate, pyruvate, and lactate-glucose ratio were significantly lower in the pH-stat group. This strategy was associated with a faster rise of brain tissue temperature and reoxygenation on reperfusion, which is likely secondary to improved cerebral perfusion. CONCLUSIONS During cardiopulmonary bypass before and after a period of hypothermic circulatory arrest, acid-base management according to the pH-stat principles seemed to be associated with less derangements in cerebral metabolism, lower intracranial pressures, and excellent behavioral recovery and survival outcome. Because there is strong evidence of the beneficial metabolic effects related to this method, further studies using an experimental model of combined HCA and embolic brain injury are required to exclude a possible increased risk of cerebral embolism associated with the pH-stat strategy.

Topical head cooling during rewarming after experimental hypothermic circulatory arrest

BACKGROUND The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest. METHODS Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37 degrees C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37 degrees C. RESULTS The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group. CONCLUSIONS Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.

Cold retrograde cerebral perfusion improves cerebral protection during moderate hypothermic circulatory arrest: A long-term study in a porcine model

BACKGROUND Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest. METHODS Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups. CONCLUSIONS Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.

Immediate and Intermediate Outcome After Off-Pump and On-Pump Coronary Artery Bypass Surgery in Patients With Unstable Angina Pectoris

BACKGROUND We have evaluated the immediate and intermediate outcome after off-pump (OPCAB) and conventional on-pump coronary artery bypass surgery (CCAB) in patients with unstable angina pectoris requiring nitrates infusion until arrival in the operating room. METHODS A consecutive series of 153 and 161 patients with unrelenting angina pectoris underwent CCAB and OPCAB, respectively. Conversion from OPCAB to beating heart surgery with perfusion occurred in 4 patients. RESULTS The OPCAB patients had a significantly higher operative risk than CCAB patients (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 13.8 +/- 12.8% vs 10.5 +/- 10.0%, p = 0.005). In the overall series, a lower 30-day postoperative mortality was observed among OPCAB patients (1.9% vs 3.9%, p = 0.33), the difference increased along the logistic EuroSCORE tertiles (upper tertile: 3.2% vs 9.5%, p = 0.14), but failed to reach statistical significance. Similar results have been observed among one-to-one propensity score matched pairs. The results of three surgeons who treated most of their patients (96.9%) with OPCAB were compared with those of three surgeons who used, in most of cases (97.1%), the CCAB technique. When adjusted for logistic EuroSCORE, patients operated on by CCAB surgeons had a significantly higher 30-day postoperative mortality (7.1% vs 2.1%, p = 0.04; odds ratio [OR] 10.143; 95% confidence interval [CI] 1.084 to 94.945) as well as a higher risk of combined adverse events (47.1% vs. 35.1%, p = 0.009; OR 2.586; 95% CI 1.274 to 5.250). CONCLUSIONS This study provided further evidence on the safety and efficacy of OPCAB in the treatment of high-risk patients. A dedicated approach to OPCAB seems to provide particularly good results. Such findings further support a more confident approach with OPCAB in these patients.

Lamotrigine plus leukocyte filtration as a neuroprotective strategy in experimental hypothermic circulatory arrest

BACKGROUND Lamotrigine and leukocyte filtration seem to improve cerebral protection during experimental hypothermic circulatory arrest (HCA). This study was performed to evaluate whether their combined use may further improve cerebral protection. METHODS Twenty-four pigs undergoing 75-minute period of HCA at 20 degrees C were randomly assigned to receive saline; lamotrigine (20 mg/kg) before HCA (L); or lamotrigine (20 mg/kg) before HCA plus leukocyte filtration before and after HCA (L + LF). RESULTS Seven animals (87%) in the L + LF group, 4 (50%) in the L group, and 3 (37%) in the control group were alive on the seventh postoperative day. The median electroencephalogram burst recovery was 94% in the L + LF group (p = 0.024 versus control group), 81% in the L group, and 64% in the control group. Among the surviving animals, the median behavioral scores were 9, 9, and 6 at the seventh day, respectively (p = 0.005 between the L + LF group and the control group). The median histopathologic score was 14 in the L + LF group (p = 0.046 versus control group), 14.5 in the L group (p = 0.062 versus control group), and 21 in the control group. CONCLUSIONS Lamotrigine has neuroprotective effect during HCA. The combined use of lamotrigine and LF may further improve the survival outcome.

Determinants of mortality after hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE Beside neurological morbidity, mortality is a relevant end-point of experimental porcine model of hypothermic circulatory arrest (HCA) and this study was conducted to identify the determinants for postoperative death. METHODS One hundred and thirty-five pigs underwent a 75-min period of HCA at 20 degrees C to evaluate the efficacy of different methods of cerebral protection. RESULTS Survival rate at 7-day follow-up was 52%. Lower oxygen extraction, oxygen consumption/kg, and venous lactate at the end of cooling and higher oxygen delivery rates were significantly associated with better outcome. Logistic regression showed that the oxygen consumption/kg at the end of cooling was the only predictor of mortality (P=0.046). Animals with an oxygen consumption/kg rate less than 1.43 ml/min per kg at the end of cooling had a mortality rate of 28%, whereas it was 50% among animals with an oxygen consumption/kg rate higher or equal to 1.43 ml/min per kg (P=0.020). The latter had even an increased 1-day mortality rate (40% vs. 26%) (P not significant). The mortality rate after anesthesia induction with ketamine plus 100% of oxygen was 38%, 45% after anesthesia induction with ketamine plus 35% oxygen, and 53% after anesthesia with medetomidine plus 35% oxygen (P not significant). CONCLUSIONS Parameters of oxyhemodynamics should be monitored especially from the induction of anesthesia to the end of cooling before a 75-min period of HCA. The use of medetomidine and/or 35% of oxygen at induction of anesthesia should be avoided in favor of ketamine plus 100% of oxygen.

Increase of Intracranial Pressure after Hypothermic Circulatory Arrest in a Chronic Porcine Model

Objective: An increase in intracranial pressure has been shown to threaten the outcome of patients with ischemic or traumatic brain injury. Its impact on the outcome of pigs undergoing hypothermic circulatory arrest has been evaluated in this study. Design: Fifty-six pigs underwent a 75-min period of hypothermic circulatory arrest at 20°C. Intracranial pressure, cerebral microdialysis, hemodynamic and metabolic parameters were monitored throughout the experiment. The animals were allowed to survive until the 7th postoperative day and, then, electively killed. Results: The 7-day survival rate was 60.7%, and among survivors, 20 of them (58.8%) developed brain infarction. A significant increase in intracranial pressure as compared with the baseline level was observed since the end of cooling ( p = 0.047) and the difference became larger during all the postoperative intervals ( p < 0.0001). Animals that died postoperatively tended to have higher intracranial pressure levels during all the postoperative intervals, but such a difference reached significance only at the 4-h postoperative interval ( p = 0.040). The same tendency was observed among animals that survived until the 7th postoperative day and that developed brain infarction or not, but the difference between these two groups did not reach statistical significance. The animals that died or developed postoperatively brain infarction had higher intracranial pressure values postoperatively as compared with those that survived without developing brain infarction and such a difference reached significance at the 2-h ( p = 0.015) and 4-h postoperative intervals ( p = 0.035). The peak intracranial pressure was 17.2 mmHg (IQR, 13.7-20.8) in animals that died or developed brain infarction and 14.1 mmHg (IQR, 11.8-16.4) in those that survived 7 days without developing brain infarction ( p = NS). Conclusion: Intracranial pressure increases significantly after 75 min of experimental hypothermic circulatory arrest and such an increase is associated with a high risk of postoperative death and brain infarction.

EEG burst recovery is predictive of brain injury after experimental hypothermic circulatory arrest

Objective--To evaluate whether electroencephalography (EEG) recovery could be considered a reliable marker of brain injury after experimental hypothermic circulatory arrest (HCA). Design--Cortical electrical activity was registered before and after a 75-min period of HCA in 27 pigs that survived 7 days after the experiment. The sum of EEG bursts was counted as a percentage of the sum of artifact-free bursts and suppressions, and this percentage was used as a measure of EEG activity in the analysis. Results--Brain infarction developed in 13 animals (48.1%), in 12 cases (44.4%) having involved the cortex, in 1 case the thalamus (3.7%) and in another the hippocampus (3.7%). The mean EEG burst percentage significantly correlated with the total brain histopathological score (ρ = −0.588, P = 0.001). EEG burst percentage from the 2 h 20 min to the 7 h 20 min interval correlated with the total brain histopathological score and with the cortex, brainstem and cerebellum scores. The mean EEG burst percentage rate was higher, but not significantly, among the animals without brain infarction (38.5% vs 32.4%), but such a difference was significant at the 3 h 20 min postoperative interval (P = 0.02). The mean EEG burst percentage significantly correlated with brain glucose concentration at the 1 h interval (ρ = 0.387; P = 0.046), brain lactate concentration at the 2 h interval (ρ = −0.431; P = 0.025), and the brain lactate/glucose ratio at the 1 h 30 min interval from the start of rewarming (ρ = −0.433; P = 0.024). Conclusion--A decreased EEG burst percentage seems to be associated with an increased risk of developing histologically evident brain ischemic injury in the cortex, brainstem and cerebellum after experimental HCA.