Desflurane Improves Neurologic Outcome after Low-flow Cardiopulmonary Bypass in Newborn Pigs

Background: Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB.

Methods: Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22[degrees]C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed.

Results: Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively.     

Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs

BACKGROUND: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model. METHODS: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19 degrees C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined. RESULTS: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group. CONCLUSIONS: Desflurane-based anesthesia yields hemodynamics during CPB with DHCA that are similar to those with fentanyl-based anesthesia. However, desflurane-based anesthesia improves neurologic and histologic outcomes of CPB-DHCA in comparison with outcomes with fentanyl-based anesthesia.     

Desflurane Confers Neurologic Protection for Deep Hypothermic Circulatory Arrest in Newborn Pigs

Background: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model.

Methods: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19[degrees]C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined.

Results: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group.     

Modified ultrafiltration may not improve neurologic outcome following deep hypothermic circulatory arrest.

OBJECTIVE: Modified ultrafiltration (MUF) improves systolic blood pressure and left ventricular performance, as well as lowering transfusion requirements, after cardiopulmonary bypass (CPB). MUF has also been shown to enhance acute cerebral metabolic recovery after deep hypothermic circulatory arrest (DHCA), but whether this improves neurologic outcome is unknown. METHODS: Sixteen neonatal piglets underwent CPB and 90 min of DHCA. The hematocrit was maintained between 25 and 30%. Alpha-stat blood gas management was used. After separation from CPB, animals were randomized to 15 min of MUF (n = 8) or no intervention (n = 8). Neurologic injury was assessed with behavior scores and histologic examination. Standardized behavior scores were obtained on post-operative days 1, 3, and 6 (0 = no deficit to 95 = brain death). The percentage of injured neurons by hematoxylin and eosin staining and the degree of reactive astrocytosis by glial filbrillary acidic protein (GFAP) immunohistochemistry were assessed to determine histologic scores in the neocortex and hippocampus (0 = no injury to 4 = diffuse injury). RESULTS: There were no statistically significant differences between groups during CPB. After MUF, the hematocrit was significantly higher (40% +/- 5.7 vs. 28% +/- 3.9, P < 0.001). There were no significant differences in behavior scores between groups (p > 0.1). There was resolution of deficits by day 6 in all animals. Neuronal injury was present in 81% (13/16) of the animals with no statistically significant differences between groups in incidence or severity. CONCLUSIONS: Use of MUF after DHCA does not prevent neuronal injury or improve neurologic outcome in this neonatal swine model.     

Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs

OBJECTIVES: Deep hypothermic circulatory arrest (DHCA) widely used during neonatal heart surgery, carries a risk of brain damage. In adult normothermic ischemia, brain cells in certain regions die, some by necrosis and others by apoptosis (programmed cell death). This study characterized regional brain cell death after DHCA in newborn pigs. METHODS: Eighteen piglets underwent 90 minutes of DHCA and survived 6 hours, 2 days, or 1 week. Six piglets underwent surgery alone or deep hypothermic cardiopulmonary bypass and survived 2 days. Three piglets received no intervention (control). Brain injury was assessed by neurologic and histologic examination and correlated with perioperative factors. Apoptosis and necrosis were identified by light microscopic analysis of cell structure and in situ DNA fragmentation (TUNEL). RESULTS: All groups subjected to DHCA had brain injury by neurologic and histologic examination, whereas the other groups did not. DHCA damaged neurons in the neocortex and hippocampus and occasionally in the striatum and cerebellum. Damaged neurons in the neocortex were mainly apoptotic and in the hippocampus, a mixture of necrotic and apoptotic neurons. Apoptosis and necrosis were apparent in all DHCA groups even though neurologic deficits improved over the week's survival. Neocortical and hippocampal damage correlated with blood glucose, hematocrit, and arterial PO(2) during and after cardiopulmonary bypass. CONCLUSIONS: In neonates, neocortical and hippocampal neurons are selectively vulnerable to death after DHCA. Both apoptosis and necrosis contribute to neuronal death, beginning early in reperfusion and continuing for days. These data suggest the need for several neuroprotective strategies tailored to the region and death process, initiated during the operation and continued after the operation.     

Deep Brain Hyperthermia While Rewarming from Hypothermic Circulatory Arrest

Abstract   Background: Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming. Methods: Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 °C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 °C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded. Results: During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 ± 0.7 vs. 32.3 ± 0.7 p < 0.05, respectively, 40 minutes: 37.5 ± 0.3 vs. 34.7 ± 0.8 p < 0.05, respectively). Conclusion: Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 °C and NPT should be closely monitored.     

Sub-MAC concentrations of desflurane do not inhibit hypoxic pulmonary vasoconstriction in anesthetized piglets

PURPOSE: In vitro, halogenated agents reduce the pulmonary vasoconstrictor response to alveolar hypoxia in isolated perfused lungs. However, studies in intact animals have been less convincing. The aim of the present study was to assess the effect of sub-MAC concentrations of desflurane on hypoxic pulmonary vasoconstriction (HPV) in anesthetized piglets using the pressure/cardiac output relationship (P/Q). METHODS: Eleven large white piglets were anesthetized and ventilated mechanically, alternatively in hyperoxia (FIO2=0.4) and in hypoxia (FIO2=0.12). Multipoint plots of pulmonary arterial pressure (PAP), or differences between PAP and left atrial pressure (LAP) against Q were generated by gradual inflation of a balloon advanced into the inferior vena cava. P/Q relationships were established in hyperoxia and in hypoxia at baseline, and then with gradual concentrations of desflurane. RESULTS: In hypoxia, pressure gradients (PAP-LAP) increased significantly at every level of Q, demonstrating active pulmonary vasoconstriction. Desflurane did not affect these P/Q relationships either in hyperoxia, or in hypoxia, when compared with baseline. CONCLUSION: Desflurane at a clinically relevant dose has no significant effect on HPV in anesthetized piglets.     

The Effect of Cardiopulmonary Bypass and Hypothermic Circulatory Arrest on Hepatic Histology in Newborn Animals: An Experimental Study

Still little is known about the effect of cardiac surgery on neonatal hepatic tissue. We examined the effect of cardiopulmonary bypass (CPB) and the effect of deep hypothermic circulatory arrest (DHCA) on neonatal hepatic tissue. Liver biopsies of neonatal piglets were taken after CPB (n = 4), after DHCA (n = 5), and after surgery without CPB (non‐CPB; n = 3). Additionally, findings were compared to those of control piglets (n = 9). The liver specimens were fixed, stained with hematoxylin and eosin, and scored regarding inflammatory reaction, hepatocellular edema, and apoptosis. Inflammation score of treated groups was higher than in control; CPB 2.5 ± 0.5, DHCA 1.6 ± 0.4, non‐CPB 1.2 ± 0.6, control 0.4 ± 0.3 (P < 0.001 CPB and DHCA vs. control; P < 0.05 non‐CPB vs. control). Hepatic cell edema was more evident after DHCA (score 2.0 ± 0.4 vs. 0.2 ± 0.3 in control and 0.6 ± 0.5 after CPB; P < 0.001 and P < 0.05, respectively). The highest apoptotic cell count was in the non‐CPB group (22.3 ± 6.3 vs. 11.4 ± 3.6 in control and 8.9 ± 5.4 after CPB; P < 0.05). The present study showed that (i) surgical trauma induces hepatic cell apoptosis; (ii) CPB increases hepatic inflammatory reaction; and (iii) DHCA amplifies hepatic cell edema.     

幼猪深低温体外循环最适区域性脑灌注流量的实验研究

目的探索幼猪在深低温体外循环中的最适区域性脑灌注（RCP）流量,为先天性心脏病（先心病）小儿患者术中脑保护策略提供理论基础。方法20只健康幼猪,年龄23．7±2．1d,体重6．4±0．6kg,采用随机数字表法分为4组,每组各5例。对照组为单纯深低温停循环（DHCA组）;实验组按不同RCP流量分为3组：RCP25组,流量为25．9±3．0ml（kg·min）;RCP50组,流量为49．7士1．8ml／（kg·rain）;RCP80组,流量为79．5±0．9ml／（kg·min）;通过检测血浆中建立CPB前（T1）、DHCA或RCP前（T2）、RCP结束后10min（T3）、停机前（T4）、CPB结束后1h（Ts）以及2h（T5）6个时间点检测血浆中的S-100β蛋白、神经元特异性烯醇化酶（NSE）的浓度、脑氧摄取率（CEOz）及大脑皮质半胱天冬氨酸酶3（caspase3）的含量,评估不同RCP流量的脑保护效果。结果各组幼猪血浆中S-100β蛋白和NSE的浓度于T4时明显升高,并于T5时达到高峰（P〈0．05）;RCP50组血浆中S-100β蛋白和NSE的浓度从T4时开始明显低于DHCA组和RCP80组（P〈O．05）,与RCP2。组相比,其差异无统计学意义（P〉0．05）。各组CEO2在T1时差异无统计学意义（P〉0．05）,在T2时明显降低（P％0．05）。DHCA组、RCPzs组和RCP50组的CEO2在T3时开始升高,RCP20组在T3时稍微下降,但其差异无统计学意义（P〉0．05）;从T4开始,RCP25组和RCPj。组的CEO。与DHcA组和RCP80组更接近于基础值（T1）（P〈0．05）。大脑皮质中caspase3的含量在3种不同流量的RCP组明显低于DHCA组（F=23．54,P〈0．01）,其中RCP25组及RCP5。组明显低于RCP80组（F=23．54,P〈0．01）,而RCP2s组与RCP50组的caspase3含量差异无统计学意义（P〉0．05）。结论在我们建立的幼猪深低温体外循环模型中,RCP最适灌注流量为25～50ml／（kg·rain）,并且趋向于50ml／（kg·rain）。     

Apoptotic neuronal death following deep hypothermic circulatory arrest in piglets

BACKGROUND: Deep hypothermic circulatory arrest (DHCA), as used in infant heart surgery, carries a risk of brain injury. In a piglet DHCA model, neocortical neurons appear to undergo apoptotic death. Caspases, cytochrome c, tumor necrosis factor (TNF), and Fas play a role in apoptosis in many ischemic models. This study examined the expression of these factors in a DHCA piglet model. METHODS: Thirty-nine anesthetized piglets were studied. After cardiopulmonary bypass (CPB) cooling of the brain temperature to 19 degrees C, DHCA was induced for 90 min, followed by CPB rewarming. After separation from CPB, piglets were killed at 1, 4, 8, 24, and 72 h and 1 week. Caspase-8 and -3 activity, and concentrations of TNF-alpha, Fas, Fas-ligand, cytochrome c, and adenosine triphosphate (ATP) were measured in the neocortex by enzymatic assay and Western blot analysis. Caspase-8 and -3 activity and cell death were examined histologically. Significance was set at P < 0.05. RESULTS: In neocortex, damaged neurons were not observed in control (no CPB), rarely observed in CPB (no DHCA), and rarely observed in the DHCA 1-h, 4-h, and 1-week reperfusion groups. However, they were seen frequently in the DHCA 8-, 24-, and 72-h reperfusion groups. Although neuronal death was widespread 8-72 h after DHCA, cortical ATP concentrations remained unchanged from control. Both caspase-3 and -8 activities were significantly increased at 8 h after DHCA, and caspase-3 concentration remained elevated for as long as 72 h. Caspase-3 and -8 activity was also observed in damaged neocortical neurons. Cytosolic cytochrome c and Fas were significantly expressed at 1 h and 4 h after DHCA, respectively. Fas-ligand and TNF-alpha were not observed in any group. CONCLUSION: After DHCA, induction of apoptosis in the neocortex occurs within a few hours of reperfusion and continues for several days. Increased Fas, cytochrome c, and caspase concentrations, coupled with normal brain ATP concentrations and apoptotic histologic appearance, are consistent with the occurrence of apoptotic cell death.     

Pediatric physiologic pulsatile pump enhances cerebral and renal blood flow during and after cardiopulmonary bypass

Controversy over benefits of pulsatile flow after pediatric cardiopulmonary bypass (CPB) continues. Our study objectives were to first, quantify pressure and flow waveforms in terms of hemodynamic energy, using the energy equivalent (EEP) formula, for direct comparisons, and second, investigate effects of pulsatile versus nonpulsatile flow on cerebral and renal blood flow, and cerebral vascular resistance during and after CPB with deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model. Fourteen piglets underwent perfusion with either an hydraulically driven dual-chamber physiologic pulsatile pump (P, n = 7) or a conventional nonpulsatile roller pump (NP, n = 7). The radiolabeled microsphere technique was used to determine the cerebral and renal blood flow. P produced higher hemodynamic energy (from mean arterial pressure to EEP) compared to NP during normothermic CPB (13 +/- 3% versus 1 +/- 1%, p < 0.0001), hypothermic CPB (15 +/- 4% versus 1 +/- 1%, p < 0.0001) and after rewarming (16 +/- 5% versus 1 +/- 1%, p < 0.0001). Global cerebral blood flow was higher for P compared to NP during CPB (104 +/- 12 ml/100g/min versus 70 +/- 8 ml/100g/min, p < 0.05). In the right and left hemispheres, cerebellum, basal ganglia, and brainstem, blood flow resembled the global cerebral blood flow. Cerebral vascular resistance was lower (p < 0.007) and renal blood flow was improved fourfold (p < 0.05) for P versus NP, after CPB. Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.     

Large-dose pretreatment with methylprednisolone fails to attenuate neuronal injury after deep hypothermic circulatory arrest in a neonatal piglet model

Conflicting results have been reported with regard to the neuroprotective effects of steroid treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). We evaluated the mode and severity of neuronal cell injury in neonatal piglets after prolonged DHCA and the possible neuroprotective effect of systemic pretreatment (>6 h before surgery) with large-dose methylprednisolone (MP). Nineteen neonatal piglets (age, <10 days; weight, 2.1 +/- 0.5 kg) were randomly assigned to 2 groups: 7 animals were pretreated with large-dose systemic MP (30 mg/kg) 24 h before surgery, and 12 animals without pharmacological pretreatment (saline) served as control groups. All animals were connected to full-flow CPB with cooling to 15 degrees C and 120 min of DHCA. After rewarming to 38.5 degrees C with CPB, animals were weaned from CPB and survived 6 h before they were killed, and the brain was prepared for light and electron microscopy, immunohistochemistry, and TUNEL-staining. Quantitative histological studies were performed in hippocampus, cortex, cerebellum, and caudate nucleus. Systemic pretreatment with large-dose MP lead to persistent hyperglycemia but no significant changes of cerebral perfusion. Necrotic and apoptotic neuronal cell death were detected in all analyzed brain regions after 120 min of DHCA. In comparison to the control group, large-dose pretreatment with systemic MP lead to an increase of necrotic neuronal cell death and induced significant neuronal apoptosis in the dentate gyrus of the hippocampus (P = 0.001). In conclusion, systemic pretreatment with large-dose MP fails to attenuate neuronal cell injury after prolonged DHCA and induces regional neuronal apoptosis in the dentate gyrus.     

The optimal flow rate for antegrade cerebral perfusion during deep hypothermic circulatory arrest

The aim of this study is to compare cerebral protection using antegrade cerebral perfusion (ACP) with various flow rates during deep hypothermic circulatory arrest (DHCA) in a piglet model. Twenty‐three piglets were randomized to five groups: the control group (n = 3), DHCA group (n = 5), ACP25 group (n = 5), ACP50 group (n = 5), and ACP80 group (n = 5). Three control piglets did not undergo operations. Twenty piglets underwent cardiopulmonary bypass (CPB) and DHCA for 60 min at 20°C. ACP was conducted at 0, 25, 50, and 80 mL/kg/min in the DHCA, ACP25, ACP50, and ACP80 group, respectively. Serum S‐100B protein and neuron‐specific enolase were monitored, and brain tissues were assayed for the activities of caspase‐3 and stained for the evidence of apoptotic cellular injury. Rise in serum S‐100B level (post‐CPB—pre‐CPB) in the ACP50 group was significantly lower than that in the ACP80 group (P = 0.001). Caspase‐3 levels were significantly elevated in the ACP80 group compared with the ACP25 (P = 0.041) and ACP50 group (P = 0.01), while positive terminal deoxyneucleotidyl transferase‐mediated biotin‐dUTP nick end labeling reaction scores in the ACP80 group were significantly higher than those in the ACP25 (P = 0.043) and ACP50 group (P = 0.023). Cerebral protection effects of ACP at 25 and 50 mL/kg/min were superior to that of ACP at 80 mL/kg/min as determined by cerebral markers, immunology, and histology.     

地氟烷在二尖瓣置换手术中对缺血再灌注心肌的保护作用

在心脏外科手术中心肌缺血再灌注(ischemia-reperfusion,I-R)损伤的防治是急需解决的问题。缺血预处理(ischemic preconditioning,IPC)具有心肌保护作用[1,2]。研究显示挥发性麻醉药也具有类似IPC的麻醉药预处理(anesthetic-induced preconditioning,APC)作用[3,4],能减轻I-R后     

血管紧张素受体的表达在地氟醚预处理心肺转流前后的变化

目的　研究血管紧张素受体Ⅰ型、Ⅱ型 (AT1、AT2 )在地氟醚预处理心肺转流 (CPB)前后的变化。方法　选择行瓣膜置换术病人 2 0例 ,随机分为两组 :D组CPB前吸入 6 %～ 9%地氟醚 ,持续时间不少于 30min ;F组以芬太尼为主行全凭静脉麻醉。分别于CPB前后取右心耳组织约5 0mg ,逆转录聚合酶链式反应 (Rt PCR)测其中AT1、AT2受体的基因表达。 结果　两组病人在CPB前后AT1受体均有表达 ,组内比较无显著差异 (P >0 0 5 ) ,组间比较差异显著 ,即F组高于D组 (P<0 0 1 ,P <0 0 5 ) ;CPB前两组病人的AT2受体均无表达 ,CPB后均见AT2受体表达 ,以D组显著高于F组 (P <0 0 1 )。结论　血管紧张素受体参与了地氟醚预处理对缺血 再灌注心肌的影响     

Utility of near-infrared spectroscopic measurements during deep hypothermic circulatory arrest

BACKGROUND: Near-infrared spectroscopy (NIRS) is used to monitor cerebral oxygenation during cardiac surgery. However, interpretation of the signals is controversial. The aim of the study was to determine which NIRS variable best correlated with brain damage as assessed by animal behavior and neurohistologic score and to compare the accuracy of NIRS and magnetic resonance spectroscopy (MRS) in predicting brain injury. METHODS: Forty 5-week-old piglets underwent 60 minutes of deep hypothermic circulatory arrest (DHCA) at 15 degrees C. Changes in brain adenosine triphosphate (ATP), phosphocreatine (PCr), and intracellular pH (pHi) were determined by MRS and correlated to changes in oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome a,a3 (CytOx) NIRS signals. Brains were fixed on day 4 and examined using a neurohistologic score. RESULTS: Reductions in CytOx and HbO2 values were correlated closely with decreases in ATP, PCr, and pHi. The changes in CytOx and PCr showed the strongest correlation (r = 0.623). Maximal CytOx reduction during DHCA of more than -25 microM * differential pathlength factor (DPF) predicted brain damage with a sensitivity of 100% and a specificity of 75%. The histologic score was also correlated with a decrease in ATP (r = -0.52 for CytOx; r = -0.32 for ATP); HbO2, PCr, and pHi showed no correlations. CONCLUSIONS: Reduction in CytOx correlates with decreased brain energy state and predicts histologic brain injury after DHCA with a high sensitivity. These data suggest that the level of CytOx could be a very important predictor of brain damage during DHCA.     

Cerebral air emboli differentially alter outcome after cardiopulmonary bypass in rats compared with normal circulation

BACKGROUND: Cerebral air emboli (CAE) are thought to contribute to adverse cerebral outcomes following cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to investigate the effect of escalating volumes of CAE on survival and neurologic and histologic outcomes. In addition, the effect of xenon administration during CAE on these outcomes was determined. METHODS: With institutional review board approval, four groups were studied (n = 15). In two CPB-CAE groups, rats were subjected to 90 min CPB with 10 repetitively administered CAE. Rats in two sham-CAE groups were also exposed to CAE but not to CPB. Rats were randomly assigned to sequential dose cohorts receiving CAE ranging from 0.2 to 10 microl in a dose-escalating fashion. Groups were further subdivided into xenon (56%) and nitrogen groups. Rats with severe neurologic damage were killed; others were neurologically tested until postoperative day 7, when infarct volumes were determined. Survival and neurologic and histologic outcomes were tested with logistic regression analyses (P < 0.05). RESULTS: This study demonstrates a dose-dependent relation between CAE volumes and survival, neurologic outcome, and histologic outcome. For all outcomes, CPB adversely affected the dose-effect curves compared with sham-CAE groups (P < 0.05). Xenon demonstrated no impact on either outcome. CONCLUSIONS: This study describes the successful incorporation of CAE in a rodent CPB model and allows identifying suitable CAE volumes for subsequent studies. CAE exhibit a differential effect on outcome in rats undergoing CPB versus those not exposed to CPB. Perioperative administration of xenon remained without any effect on outcome.     

Cerebral Air Emboli Differentially Alter Outcome after Cardiopulmonary Bypass in Rats Compared with Normal Circulation

Background: Cerebral air emboli (CAE) are thought to contribute to adverse cerebral outcomes following cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to investigate the effect of escalating volumes of CAE on survival and neurologic and histologic outcomes. In addition, the effect of xenon administration during CAE on these outcomes was determined.

Methods: With institutional review board approval, four groups were studied (n = 15). In two CPB-CAE groups, rats were subjected to 90 min CPB with 10 repetitively administered CAE. Rats in two sham-CAE groups were also exposed to CAE but not to CPB. Rats were randomly assigned to sequential dose cohorts receiving CAE ranging from 0.2 to 10 [mu]l in a dose-escalating fashion. Groups were further subdivided into xenon (56%) and nitrogen groups. Rats with severe neurologic damage were killed; others were neurologically tested until postoperative day 7, when infarct volumes were determined. Survival and neurologic and histologic outcomes were tested with logistic regression analyses (P < 0.05).

Results: This study demonstrates a dose-dependent relation between CAE volumes and survival, neurologic outcome, and histologic outcome. For all outcomes, CPB adversely affected the dose-effect curves compared with sham-CAE groups (P < 0.05). Xenon demonstrated no impact on either outcome.     

Desflurane pharmacokinetics during cardiopulmonary bypass

OBJECTIVE: To describe the washin and washout of desflurane when first administered during cardiopulmonary bypass (CPB) for cardiac surgery. DESIGN: A single-arm prospective study. SETTING: University-affiliated hospital operating room. PARTICIPANTS: Ten adult patients presenting for cardiac surgery. INTERVENTIONS: Consenting patients presenting for cardiac surgery received anesthesia with midazolam and fentanyl. Patients were cooled to 32 degrees C on CPB, then desflurane 6% was administered and blood samples drawn repeatedly from the arterial and venous bypass cannulae as well as from the membrane oxygenator inlet and exhaust from 2 to 32 minutes of desflurane administration. Just before rewarming, final (maximum) washin samples were taken. On rewarming, desflurane was discontinued, and blood and gas samples were taken 2 to 24 minutes thereafter. MEASUREMENTS AND MAIN RESULTS: CPB time was 116 +/- 10 minutes, and ischemic time was 81 +/- 6 minutes. Mean pump flow was 4.49 +/- 0.03 L/min, and mean arterial pressure was 70.1 +/- 1 mmHg during the study period. Arterial washin of desflurane was initially rapid; arterial concentrations reached 50% of administered concentrations within 4 minutes, but then slowed, reaching 68% of inspired concentrations at 32 minutes (desflurane concentration 4.0% +/- 0.3%). Arterial washout of desflurane was more rapid; arterial concentrations fell to 18% of the maximum concentration reached within 4 minutes, and only 8% of the maximum arterial concentration was present in blood 20 minutes later. CONCLUSION: Desflurane showed rapid initial washin and washout on CPB when administration was started at 32 degrees C and stopped at time of rewarming.     

Desflurane analgesia for vaginal delivery

The use of subanaesthetic concentration of inhalational anaesthetic for vaginal delivery offers many advantages to the mother and newborn- Desflurane, with the characteristics of rapid onset and minimal metabolism, may provide better analgesia and safety for labour pain control.
Eighty healthy parturients were randomly assigned to receive either desflurane 1.0–4.5% and oxygen (n = 40) or nitrous oxide 30–60% in oxygen (n=40). Analgesia was assessed using a score from 0 (no relief) Lo 4+ (excellent analgesia), amnesia for the delivery, blood loss were recorded. Neonates were evaluated by Apgar scores and neurologic and adaptive capacity scores (NACS). Data were analyzed for statistical significance using Student's l-test or Chi-square when appropriate.
Analgesia scores were similar for both groups with more amnesia in desflurane group (23% vs 0% P <0.05). Blood loss did not differ significantly, 364 ml for the desflurane group and 335 ml for the nitrous oxide group. There were no significant differences for neonatal Apgar score at 1 min or at 5 min or the NACS at 2 hr or 24 hr between the two groups.
We conclude that desflurane in subanaesthetic doses is safe and effective inhalation agent for normal delivery but might be associated with amnesia.