Accidental hypothermia with cardiac arrest: recovery following rewarming by cardiopulmonary bypass.

A 22-year-old man eventually had a good neurologic recovery following prolonged coma after extracorporeal rewarming from profound hypothermia (24 degrees C) due to exposure. The patient was in full arrest for 60 minutes prior to institution of cardiopulmonary bypass (CPB). Total bypass time was 50 minutes. Cardiopulmonary bypass is the current rewarming method of choice for severe hypothermia associated with a persistent nonperfusing cardiac rhythm. CPB provides the most rapid core rewarming with the additional benefit of circulatory support during the period of cardiac instability.     

Plasma epinephrine levels in resuscitation with cardiopulmonary bypass

Since the highest plasma epinephrine levels have been recorded during resuscitation, we evaluated the isolated effect of cardiac arrest upon adrenomedullary secretion. We determined plasma epinephrine in dogs resuscitated with cardiopulmonary bypass (CPB) after cardiac arrest periods of 12 (CPB-12; n = 4) or 16 min (CPB-16; n = 5). Through 2 h of CPB and the following 6 h of critical care, there was no difference between CPB-12 and CPB-16 regarding most cardiopulmonary functional variables. Plasma epinephrine was markedly elevated immediately after initiation of CPB (p less than .01 at 1 min CPB vs. basal) and returned rapidly to basal concentrations. Comparison of plasma epinephrine levels between CPB and standard CPR groups showed that responses to cardiac arrest were similar (p greater than .05 at 1 min CPB vs. 11.5 min CPR). We conclude that cardiac arrest is the main or sole determinant of the plasma epinephrine elevation of resuscitation.     

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding

OBJECTIVE: Cardiopulmonary bypass is known to result in a reduction in the plasma binding of drugs. The resulting effect on the hepatic clearance of drugs with low extraction is well understood. However, the situation with those that are highly extracted is less clear. Studies were, therefore, undertaken with one such drug, propofol, for which plasma binding was changed during cardiac surgery with cardiopulmonary bypass. METHODS: After induction of anesthesia with midazolam in 19 patients, propofol was infused continuously at a rate of 4 mg. kg(-1). h(-1) during surgery. Propofol's concentration was measured by HPLC in blood samples collected from the radial artery and hepatic vein during surgery at predetermined intervals. The drug's unbound fraction in arterial plasma was estimated via equilibrium dialysis. RESULTS: The total concentration of propofol in blood was unchanged during surgery except shortly after the initiation of cardiopulmonary bypass. By contrast, the fraction of unbound propofol in blood increased by 2-fold during cardiopulmonary bypass and then decreased after the completion of cardiopulmonary bypass. The hepatic extraction ratio of propofol was greater than 0.8 and remained constant throughout surgery. The ratio of propofol concentration in erythrocytes to that in blood increased by 1.6-fold during cardiopulmonary bypass. CONCLUSIONS: During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.     

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition.

The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased. Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per m2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).     

异丙酚对体外循环期间脑氧供需平衡的影响

目的 :探讨异丙酚对体外循环期间脑氧供需平衡的影响。方法 :将 30例拟在体外循环 (CPB)下行瓣膜置换术的病人随机分为对照组和异丙酚组 ,对照组用芬太尼维持麻醉 ,异丙酚组则用异丙酚 ,观察两组病人颈静脉血氧饱和度 (SjO2 )、动脉和颈内静脉血氧含量差 (Da -vO2 )、脑氧摄取率 (CEO2 )的变化。结果 :复温时异丙酚组SjO2 显著高于对照组 ,Da -vO2 及CEO2 显著低于对照组 ,且复温时SjO2 与CPB前相比 ,差异无统计学意义 (P >0 .0 5 )。结论 :异丙酚能够防止CPB时脑氧供需失衡。护理上应充分做好术前准备 ,熟练配合手术 ,以缩短CPB及低温时间。     

Prospective study on cardiopulmonary bypass prime reduction and its effect on intraoperative blood product and hemoconcentrator use

PURPOSE: Evaluate the feasibility and clinical significance of crystalloid prime reduction during the initiation of cardiopulmonary bypass (CPB) using a modified bridge on the cardioplegia delivery system. METHODS: Prospective trial of crystalloid prime reduction using a standard Duraflow-coated CPB circuit and Vanguard 2:1 cardio plegia delivery system. Standard prime volume was 1500 cc of Plasmalyte. Prime was reduced via the bridge in the cardioplegia system during initiation of CPB. Packed red blood cells (PRBC) were transfused for hematocrit (Hct) less than 24% while rewarming. A hemoconcentrator was used if the patient's circulating blood volume exceeded 150% of calculated. All data were prospectively collected. RESULTS: Two hundred and twenty-two consecutive patients undergoing cardiac surgery utilizing CPB were evaluated. There were 107 patients with normal prime volume (NPV) and 115 patients with reduced prime volume (RPV). There was no significant difference in sex, mean age, weight, body surface area (BSA), pre-op Hct, procedure time or procedure between the two groups. There was no difference in total crystalloids infused by the anesthetists (average NPV 1205 cc versus RPV 1148 cc). The average RPV was 622 cc (range 400-1100 cc) or a 59% reduction. Post-op Hct revealed no difference (NPV 28% versus RPV 29%). There was a 24% reduction in patients requiring PRBC (NPV n=23 versus RPV n=18). The use of hemoconcentrators was reduced by 49% (NPV n=18 versus RPV n =11). The average urine output for both groups exceeded 100 cc/hour while on CPB. CONCLUSION: Using a modified cardioplegia delivery system is a safe and effective method of CPB prime reduction. A RPV resulted in fewer patients requiring PRBC transfusions and fewer hemoconcentrators used. Based on our experience, we would recommend attempting to reduce prime volume in all patients undergoing CPB.     

舒芬太尼与芬太尼用于小儿先心病手术的对比研究

【目的】研究比较舒芬太尼与芬太尼在小儿先心病手术中对血流动力学、血浆儿茶酚胺的影响。【方法】选取心功能Ⅰ～Ⅱ级,无严重肝肾功能疾患的先心病患儿40例,随机分为芬太尼组（F组,n=20）和舒芬太尼组（S组,n=20）。F组麻醉诱导时给予芬太尼20μg／kg,划皮前、体外转流前分剐追加芬太尼10μg／kg;S组麻醉诱导时给予舒芬太尼2μg／kg,术中静脉持续输注舒芬太尼2μg／（kg·h）,体外转流期间1μg／（kg·h）。在麻醉诱导后（T0）、开胸前（T1）、体外转流30min（T2）和停体外转流2h（T3）等时点记录心率（HR）、平均动脉压（MAP）监测值,并在T1、T2、T3等时点采血测定血浆多巴胺及乳酸含量。【结果】F组与S组麻醉效果均较满意,但T0时点心率均明显下降;S组T1、T3时点的心率下降更为明显（P〈0．05）;F组在T2时点乳酸水平升高较S组明显（P〈0．05）。【结论】舒芬太尼与等效剂量的芬太尼均能有效抑制血浆儿茶酚胺的释放,可以安全应用于小儿先心病手术的麻醉。     

The oxygen debt during routine cardiac surgery: illusion or reality?

BACKGROUND: Patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB) are often thought to have tissue hypoxia and intraoperative oxygen debt accumulation despite the lack of sufficient data to support this assumption. METHODS AND RESULTS: Oxygen uptake and related parameters, including the plasma lactate and pyruvate concentrations, were studied during the perioperative period in a group of 15 consecutive patients who underwent coronary artery bypass graft surgery. The actual oxygen uptake (VO2) and delivery (DO2) were compared with the individual expected (computed) oxygen transport values. The mean values of DO2 and VO2 were in the range of the expected values. Our results demonstrate a leading role for body temperature in perioperative changes of oxygen consumption rate (r2=0.65, p<0.001). Plasma lactate and pyruvate did not exceed the physiological range in any patient. However, with initiation of CPB, the lactate to pyruvate (LA/PVA) ratio increased (from 9.87 +/- 2.43 at T1 to 12.08 +/- 1.51 at T2, p<0.05). The mean value of the LA/ PVA ratio was elevated during surgery. Later, upon lowering of the plasma lactate concentration in the postoperative period, the LA/PVA ratio decreased to normal values. Without any other evidence of hypoxia, this increase in the LA/PVA ratio could be explained by washout of lactate from previously hypoperfused tissues and intraoperative decrease of lactate clearance. CONCLUSION: Systemic oxygenation was not impaired during CPB, or during 18 h after surgery in the studied group of patients.     

Altered d-tubocurarine disposition during cardiopulmonary bypass surgery

Kinetics of the neuromuscular blocker d-tubocurarine (dTc) were investigated in 13 adult patients undergoing surgery involving cardiopulmonary bypass (CPB). Approximately 1 hr before CPB surgery, each received dTc as an intravenous bolus of 0.6 mg/kg and a maintenance infusion of 3 micrograms/kg/min. dTc plasma concentration-time data before CPB did not differ from those reported in normal surgical patients. There was an abrupt discontinuity in the plasma concentration-time profile with the onset of CPB, and both total and free plasma concentrations increased 400% during the period of CPB. Although computer simulations suggest that these rises in dTc plasma concentrations can be attributed to contraction in central compartment volume, there also was decreased renal and total plasma clearance of dTc together with a prolonged elimination 1 1/2, which suggests that clearance processes of dTc are also altered as a result of CPB. A 27% rise in dTc free fraction in plasma during CPB could be attributed to hemodilution associated with the CPB procedure itself. Lower doses of dTc will need to be used in patients undergoing surgery that involves CPB unless the concentration-effect relationship for dTc is so altered that higher concentrations are needed to elicit the same response as in normal patients.     

Effect of vitamin B6 administration on elevated plasma oxalic acid levels in haemodialysed patients

Abstract. Accumulation of oxalic acid resulting in elevated plasma levels is a common finding in uraemic patients. Since vitamin B₆ is an important coenzyme in oxalic acid metabolism the influence of vitamin B₆ administration on plasma oxalic acid levels was investigated.
Vitamin B₆ was administered to eight chronic haemodialysis patients with secondary hyperoxalaemia. Mean plasma oxalic acid concentration decreased from 149·5 ± 67 μmol/l to 99·0 ± 36·4 μmol/l within 2 weeks and to 93·8 ± 33·1 μmol/l after 4 weeks of pyridoxine treatment ( P <0·01) the mean reduction being 46% (32·0–56·1%). The decrease in plasma oxalic acid levels was most pronounced in patients with the highest pretreatment values. Two patients who received pyridoxine therapy prior to the beginning of the study had low initial values of plasma oxalic acid concentrations and showed no further decline.     

Metocurine kinetics in patients undergoing operations requiring cardiopulmonary bypass

Metocurine kinetics were determined in 10 patients undergoing operations requiring hypothermic cardiopulmonary bypass (CPB) and nine patients of similar age undergoing operations of similar duration but not requiring CPB. The metocurine dosage regimen was a bolus of 0.3 mg/kg given concomitantly with the commencement of an infusion at a rate of 0.04 mg/kg/hr; this regimen was designed to produce and maintain a plasma metocurine concentration associated with 95% depression of the twitch response. Metocurine kinetics were affected minimally by hypothermic CPB. The kinetic parameters including volumes of distribution at steady state of 0.35 L/kg and 0.34 L/kg and elimination clearances of 1.3 ml/min/kg and 1.1 ml/min/kg in the control and CPB groups, respectively, are in agreement with the results of others. Changes in neuromuscular blockade with the onset of CPB and the return to original blockade intensities with rewarming suggest a decreased sensitivity to the effects of metocurine at lower temperatures.     

The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide (GIP) in man

Abstract. The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide were investigated in six healthy volunteers. At the maximum infusion dose (0·5 pmol kg^-1 min^-1) a plateau concentration of 115 ± 5·0 pmol/l plasma was obtained. On discontinuation of the infusion, the half-time of disappearance was calculated to be 20·3 ± 1·2 min. The metabolic clearance rate was 2·6 ± 0·1 ml kg^-1 min^-1 and the apparent space of distribution was 75·8 ± 5·7 ml kg^-1. Blood glucose, pancreatic and gastrointestinal hormones remained at basal concentrations throughout. No side effects were noted by any of the subjects studied.     

A pilot study of the effect of antipyrine on caffeine kinetics in six healthy volunteer subjects

The potential interaction is described between caffeine and antipyrine, two drugs with a high probability of being concomitantly administered for the evaluation of liver metabolism. In order to determine the influence of antipyrine on the elimination of caffeine, salivary caffeine clearance was measured in six healthy volunteers prior to and 2 and 5 days after the administration of a single oral dose of 1000 mg of antipyrine.
Total caffeine clearance increased on average by 24% (from 1·65 to 2·05 ml/min, P =0·1) 2 days after antipyrine dosing, and 25% (from 1·65 to 2·06 ml/min, P <0·01) 5 days after the administration of antipyrine, whereas the half‐life decreased by around 24% (from 5·3 to 4 h, P =0·09) after 2 days and 26% (from 5·3 to 3·9 h, P =0·05) after 5 days. The apparent volume of distribution did not change. These results suggest that antipyrine is able to increase the elimination of caffeine, probably by means of inducing its hepatic metabolism. When both drugs are used sequentially in the same patient to assess the drug metabolizing activity of the liver, the caffeine test should be performed first.     

Liquid lung ventilation reduces neutrophil sequestration in a neonatal swine model of cardiopulmonary bypass

OBJECTIVE: Liquid lung ventilation has been demonstrated to improve cardiorespiratory function after cardiopulmonary bypass. We hypothesized that liquid lung ventilation (LLV) would decrease the pulmonary inflammatory response after cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, experimental, controlled, nonblinded study. SETTING: Animal research laboratory at a university setting. SUBJECTS: A total of 24 neonatal piglets. INTERVENTIONS: After intubation with a cuffed endotracheal tube, swine were conventionally ventilated. After surgical cannulation, each piglet was placed on conventional nonpulsatile CPB and cooled to 18 degrees C (64.4 degrees F). Subsequently, the animals were exposed to 90 mins of low-flow CPB (35 mL/kg/min). Animals were rewarmed to 37 degrees C (98.6 degrees F), removed from CPB, and ventilated for 90 min. Ten animals received conventional gas ventilation only (control), seven received initiation of LLV before CPB (prevention), and seven received initiation of LLV during the rewarming phase of CPB (treatment). After the animals were killed, the lungs were removed en bloc. The left lobe was dissected and formalin-fixed at 20 cm H2O overnight, followed by paraffin embedding. Sections were taken from the paraffin-embedded lungs. Neutrophil accumulation and lung injury were assessed by histochemical staining with leukocyte esterase and morphometrics, respectively. One hundred microscopic images were digitized from each tissue sample for lung morphometrics, and neutrophil counts were obtained from every fifth image. MEASUREMENTS AND MAIN RESULTS: Lung tissue sections showed a significantly lower number of neutrophils per alveolar area in the prevention and treatment groups than in the control group (control 681 +/- 65, prevention 380 +/- 49, treatment 412 +/- 101 neutrophils per alveolar area [cells/mm2]; p <.05 for both prevention and treatment compared with control). There were no differences in lung injury as assessed with morphometrics or hemodynamic measurements between any of the three groups. CONCLUSIONS: The data suggest that LLV reduces the CPB-induced neutrophil sequestration in the pulmonary parenchyma independent of its effects on the circulatory physiology or evidence of early lung injury.     

Gastric acid regulates the release of plasma secretin in man

Abstract. Fasting plasma secretin determined in nine healthy subjects, twelve patients with active duodenal ulcer and four with Zollinger-Ellison syndrome were 3·2±0·4, 5·1±1·2 and 20·3±1·3 pmol/l respectively (mean ±SEM). Cimetidine significantly ( P <0·05) reduced levels in those with duodenal ulcer, as did gastric aspiration in the Zollinger-Ellison group. A significant correlation ( P <0·001) was found between basal acid output and mean fasting plasma secretin. After a solid meal and subsequent liquid soft drink, no sustained mean rise in plasma secretin was observed; changes in secretin appeared to coincide in time with rapid falls in duodenal pH, though little relationship could be established between the absolute level of pH and changes in plasma secretin. The mean peak post-prandial rise in plasma secretin observed after solids was significantly ( P <0·05) greater in duodenal ulcer patients than controls (9·1±1·1 versus 6·7±0·5 pmol/l) as was the mean integrated post-prandial release (1002±110 versus 710±67 pmol min^-1 l^-1). Cimetidine reduced both rises ( P <0·05) and was associated with significantly less duodenal pH readings below 4 ( P <0·001). These results suggest that gastric acid is a major release mechanism for plasma secretin both fasting and after meals but it is likely the acid load rather than absolute pH in the duodenum which determines circulating levels.     

Pressure and oxygen debt on bypass - potential quality markers of perfusion?

No markers of quality of perfusion pressure and oxygen delivery during cardiopulmonary bypass (CPB), to complement rewarming rate, maximum temperature on rewarming, lowest haematocrit, and blood glucose, exist. Using the electronic acquisition of blood pressure on bypass (JOCAP system), the percentage of time perfusion pressure was below 30, 40, 50, 60 and 70 mmHg, average deviance, confidence interval, median, mode, standard deviation, variance, and average, maximum and cumulative oxygen debt were calculated. Numerous different readouts of achievement of maintenance of constant pressure on bypass and oxygen debt are now easily achievable with perfusion electronic data management systems. Mean, median, and mode offer poor discrimination of pressure control during CPB. Percentage of time perfusion pressure was below 30, 40, 50, 60 and 70 mmHg, average deviance, confidence interval, and standard deviation all have discriminatory power, but need clinical correlation for their significance. A composite score involving non-pressure readouts (e.g. oxygen delivery, arterial and venous saturations, and flow rates) may need to be integrated into any perfusion quality marker. Assessment of adequacy of constant perfusion pressure and oxygen delivery may allow the scientific evaluation of pressure and oxygen delivery on bypass for patients to be compared accurately. Currently, in studies involving CPB, blood pressure targets are stated with no quantitative assessment of adequacy of achievement of these targets. Electronic data monitoring during cardiopulmonary bypass, when correlated with clinical outcome, may help to provide a marker of quality of perfusion pressure during CPB and may, indeed, allow patient-specific perfusion pressure strategies to be developed.     

Kinetics of circulating hyaluronan in humans

Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA were given, separated by 90 min washout periods. Blood samples were taken before, during and after each infusion and the plasma HA concentration was determined. The deposition of HA was modelled according to a Michaelis–Menten kinetic model which included natural synthesis of HA. K_m and V_max was estimated to 0·34 ± 0·13 μgml^-1 and 3·48 ± 0·97/μmin^-1kg^-1 b.w., respectively. The endogenous input was calculated to be 24 ± 11 μg min^-1 and was found to correlate to the age of the subjects ( P < 0·05). As the baseline HA concentration was 0·031 ± 0·21 μg ml^-1, the rate of elimination was linear in the normal concentration range. The calculated V_d was about 75% higher than a weight-estimated plasma volume. The total amount of HA excreted by the kidneys during the study period was 394 ± 77 μg, which corresponded to approximately 1·7% of the total input of HA into the circulation during the experiment.     

体外循环期间Apelin-36、NO和TNF-α的变化和意义

目的:探讨体外循环期间Apelin-36、一氧化氮(NO)和肿瘤坏死因子-α(TNF-α)的变化和意义。方法:选择17例行直视下心脏手术患者,检测手术开始前(T0)、主动脉开放后即刻(T1)、主动脉开放后10 min(T2)、停机后即刻(T3)4个时间点动脉和静脉血浆中的Apelin-36、NO和TNF-α浓度。结果:与术前(T0)比较,体外循环过程中动脉血Apelin-36浓度在T1、T2和T3均升高(P0.01或P0.05);静脉血中Apelin-36浓度在T1和T2时高于T0(P0.01);动脉血NO浓度在T1时、静脉血NO浓度在T3时高于术前值(P0.01或P0.05);动脉血TNF-α浓度在T1和T3以及静脉血TNF-α浓度在T3高于术前(P0.01)。结论:体外循环可诱导血浆中Apelin-36、NO和TNF-α浓度的增加。     

Effect of Cardiopulmonary Bypass on Regional Antibiotic Penetration into Lung Tissue

The use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performed in vivo microdialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group). LVX (750 mg) was administered intravenously to all pigs immediately after surgery. For regional measurements of LVX in pulmonary concentrations, microdialysis probes were inserted in both lungs of each pig. Pigs were placed in the right lateral position. Time versus concentration profiles of unbound LVX were measured in the upper and lower lung tissue and plasma in all pigs. In all pigs, maximum concentrations (C_max) of LVX were significantly lower in the upper lung than in the lower lung (OPCAB, P = 0.035; CPB, P < 0.001). Median C_max of LVX showed a significant difference in the upper versus lower lung in the CPB group (P < 0.05). No significant difference was found in the median C_max of LVX in the upper and the lower lung in the OPCAB group (P = 0.32). Our data indicate that CPB affects perioperative regional antibiotic penetration into lung tissue. Common clinical antibiotic dosing schemes should be reevaluated in patients undergoing coronary artery bypass grafting with CPB.     

Resuscitation of the hypothermic patient

A case of cardiac arrest following hypothermia due to cold-water immersion is presented. Following rescue and initiation of cardiopulmonary resuscitation, the patient was transported by helicopter to a facility where rewarming using cardiopulmonary bypass was possible. Initial rectal temperature in the emergency department was 28 degrees C. Initial prehospital rhythm was ventricular fibrillation persisting approximately 1.5 hours until the patient was successfully cardioverted after 25 minute of femoral artery/femoral venous partial cardiopulmonary bypass rewarming. Temperature at the time of cardioversion was 30 degrees C (esophageal). Despite extended cardiac arrest and profound metabolic acidosis (pH = 6.41 at 37 degrees C), he recovered uneventfully and is neurologically normal. A protocol for the management of a patient with hypothermic cardiac arrest is included.