Comparison of meperidine and pancuronium for the treatment of shivering after cardiac surgery

Shivering after cardiac surgery can produce adverse haemodynamic and metabolic sequelae. In this study, the metabolic effects of shivering and the efficacy of treatment with meperidine or pancuronium were studied, using a metabolic cart, in 61 patients who had undergone cardiac surgery. The patients received premedication with morphine, perphenazine and diazepam or lorazepam, and were anaesthetised with fentanyl or sufentanil and diazepam. Muscle relaxation was achieved with pancuronium. Patients were monitored with a radial arterial line, pulmonary artery catheter and oesophageal and urinary bladder temperature probes. Rewarming to an oesophageal temperature of 38 degrees C was achieved before the termination of CPB and was maintained for a minimum of 15 min reperfusion time. Every 15 min after surgery, the patients' temperature at three sites (pulmonary artery, oesophagus, bladder) and shivering scores were monitored. Hourly measurements were made of haemodynamic variables (MAP, PAOP, CVP, SVR, PVR, CI), carbon dioxide production, oxygen consumption and respiratory quotient. If the patient shivered, the measurements were recorded prior to drug treatment and repeated 30 min later following randomization to either: meperidine 0.25 mg.kg-1 (Group 1), meperidine 0.5 mg.kg-1 (Group 2) or pancuronium 0.06 mg.kg-1 intravenously (Group 3). Thirty-two patients shivered and mean VO2 and VCO2 values were greater in the shivering group than in the nonshivering patients (VO2 334.8 +/- 17.6 vs. 240.5 +/- 8.8 ml.min-1; VCO2 238.8 +/- 17.2 vs 199.2 +/- 8.4 ml.min-1, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic Correlates in Infants and Children During Anaesthesia and Surgery

In 58 infants and children with body weights between 2.8 and 20.5 kg carbon dioxide production (VCO2 ml min-1) was measured during halothane anaesthesia for minor surgical procedures. In 22 cases measurements were made during both spontaneous and controlled ventilation during the same operation. A non-rebreathing circuit was used. Expired ventilation volume was measured with a dry gas meter and expired gas collected during 3-5 min in a Douglas bag. The carbon dioxide fraction of exhaled gas was determined with a sampling Gould capnograph. A respiratory quotient (RQ) of 0.8 was used to calculate oxygen consumption (VO2 ml min-1). During spontaneous breathing, regression analysis of the relationship between VCO2 and kg and between VO2 and kg showed high intercepts while corresponding relations to kg3/4 revealed an almost direct proportionality. Thus, VCO2 and VO2 ought to be related to body weight in kg3/4 in spontaneously breathing children. The mean value (+/- 1 s.d.) for VCO2 was 11.4 +/- 3.1 ml kg-3/4 and for VO2 14.2 +/- 3.9 ml kg-3/4. During controlled ventilation, the relationship between kg b.w. showed for VCO2 as well as for VO2 an almost direct proportionality with a mean value (+/- 1 s.d.) for VCO2 of 6.3 +/- 1.6 ml min-1 kg-1 and for VO2 of 7.8 +/- 2.0 ml min-1 kg-1. Prediction of VO2 for infants and children of this size could be based upon 14 X kg3/4 during halothane anaesthesia and surgery.     

Oxygen consumption after flumazenil reversal

The effect of flumazenil reversal of midazolam-induced anesthesia on whole body oxygen uptake (VO2) was investigated in a double-blind trial in 48 patients (ASA, 1 or 2) undergoing elective surgery under general anesthesia. VO2 was measured in spontaneously breathing patients during recovery from anaesthesia induced with midazolam 0.25 mg.kg-1 and maintained with nitrous oxide 60% in oxygen and halothane. The level of sedation was evaluated by a subjective score. To reverse midazolam-induced anesthesia, patients were randomly allocated to receive placebo or flumazenil (6 micrograms.kg-1). No significant changes in VO2 (160 +/- 53 vs 150 +/- 39 ml.min-1.m-2 or sedation score (2.5 +/- 1.0 vs 2.1 +/- 0.9) were observed in the placebo group. After flumazenil administration, the sedation score significantly (P less than 0.05) improved (2.9 +/- 1.0 vs 1.3 +/- 0.8) whereas no significant change in VO2 was observed (158 +/- 67 vs 157 +/- 61 ml O2.min-1.m-2). These data show that reversal of benzodiazepine effects with flumazenil resulted in no significant change in oxygen uptake.     

The effect of paralysis on oxygen consumption in normoxic children after cardiac surgery

To determine whether paralysis reduces oxygen consumption (V02) after cardiac surgery in infants, the authors measured V02 before and after paralysis in 17 sedated infants who were ventilated mechanically after cardiac surgery. Oxygen consumption was determined as being the difference between oxygen content of inspired and expired gases. The absence or presence of "movement" (breathing or repeated movement of the extremities) before paralysis was noted. For eight infants who did not "move" before paralysis, VO2 was similar before (9.1 +/- 1.2 ml . kg-1 . min-1, mean +/- SD) and after (9.0 +/- 1.5 ml . kg-1 . min-1) paralysis (P = 0.81). However, for nine infants who did "move" before paralysis, VO2 decreased from 9.2 +/- 1.4 ml . kg-1 . min-1 before paralysis to 8.0 +/- 1.4 ml . kg-1 . min-1 after paralysis (P less than 0.05). One infant in each group had an increase in VO2 greater than 10% of the baseline value (i.e., 12% and 14%). In conclusion, if breathing or repeated movement is present before paralysis, paralysis decreases VO2 by 13% in sedated infants after cardiac surgery. If repeated or regular movement is not present before paralysis, paralysis does not decrease VO2. These data suggest that in normoxic patients, muscle paralysis does not significantly alter V02 and therefore should not be used for this purpose.     

The effect of pre-oxygenation on hemodynamics and oxygen consumption

Pre-oxygenation is routinely used prior to anesthesia and intubation. In awake, premedicated patients scheduled for major aortic surgery we assessed the effects of breathing oxygen for 10 min via a loosely fitting face mask on hemodynamics and oxygen consumption (VO2). RESULTS. O2-breathing increased arterial PO2 to 51 +/- 13 kPa and decreased VO2 from 109 +/- 18 to 92 +/- 24 ml.min-1.m-2 (P less than 0.001 for both variables). This reduction of VO2 resulted from both a fall in cardiac index from 3.22 +/- 0.67 to 3.04 +/- 0.75 1.min-1/m-2 (P less than 0.05) and a decrease in arterio-venous oxygen content difference from 3.45 +/- 0.60 to 3.03 +/- 0.57 ml/dl (P less than 0.001). Systemic peripheral vascular resistance increased slightly from 1453 +/- 359 to 1538 +/- 383 dyne.s.cm-5.m-2 (P less than 0.05). CONCLUSIONS. These results indicate that an increase in F1O2 in patients without severe limitations of oxygen uptake by the lungs or oxygen transport to the tissues does not improve tissue oxygenation. We speculate that increased peripheral shunting acts to protect tissue PO2 during high arterial PO2 levels.     

Use of norepinephrine in the treatment of septic shock

The effects of noradrenaline were studied in 16 patients, with either a hyperkinetic septic shock syndrome or a septic shock resistant to dobutamine treatment. The study aimed to restore normal tissue perfusion pressure, assessed by a return to normal of urine output or blood pressure. An optimal left ventricular filling pressure, estimated by the pulmonary capillary wedge pressure, was obtained for each patient using a Swan-Ganz catheter. The administration of 10.6 +/- 0.5 micrograms.kg-1.min-1 dobutamine (starting dose: 6 micrograms.kg-1.min-1) was started when the cardiac index (CI) was less than 3.3 l.min-1.m-2 after vascular filling with plasma expanders. Patients became eligible for noradrenaline treatment when they fulfilled the following conditions: arterial systolic pressure (Pasys) less than or equal to 90 mmHg; systemic vascular resistances less than or equal to 600 dyn.s.cm-5; CI greater than 3.5 l.min-1.m-2; persistent oliguria (less than 30 ml.h-1). This drug was given at a constant rate with a starting dose of 0.5 micrograms.kg-1.min-1, increased every 10 min by 0.3 to 0.6 micrograms.kg-1.min-1 according to the effects on Pasys and hourly urine output. Eight patients received noradrenaline alone; the efficient dose was 0.9 +/- 0.2 micrograms.kg-1.min-1, and it was used for a mean 5.1 +/- 1 days. CI increased in those patients who were given both noradrenaline and dobutamine. Thirteen out of the 16 patients had a dramatic increase in urine output; only three patients remained oliguric. There were no effects on serum creatinine concentration, anion gap, intrapulmonary shunt and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of dobutamine in hyperkinetic septic shock treated with norepinephrine

A prospective study of the haemodynamic effects of dobutamine was carried out in six men and four women suffering from hyperkinetic septic shock, already treated with noradrenaline and dopamine. All ten patients had septic shock, defined as a mean arterial blood pressure of less than 70 mmHg and an urine output under 15 ml.h-1, persisting despite fluid loading, associated with positive blood cultures, increased white blood cell counts, and a septic area. Initial treatment consisted in fluid loading, so as to increase cardiac output whilst keeping pulmonary wedge pressure (Ppw) between 8 and 10 mmHg. Dopamine was then added, up to a dose of 15-20 micrograms.kg-1.min-1, in an attempt to improve coronary and renal blood flows. In patients in whom this failed, the amounts of dopamine were then decreased, down to 3 micrograms.kg-1.min-1, and replaced by noradrenaline. When patients had as steady cardiac index (CI) greater than 3 l.min-1.m-2 and a systemic arterial resistance index (RsaI) of less than 1,800 dyn.s.cm-5.m-2 for more than 60 min, they were included in the protocol. Dopamine was then replaced by increasing doses of dobutamine (0, 5, 7.5, 10, 15 and again 0 micrograms.kg-1.min-1). The usual haemodynamic parameters were measured and calculated once a steady state had been obtained at each dose (within 20 to 30 min). Ppw was kept between 8 and 10 mmHg by fluid loading with a 4% albumin solution. At the beginning of the study, patients had a mean blood pressure of 78 +/- 6 mmHg, a CI of 4.8 +/- 1.5 l.min-1.m-2 and a RsaI of 1,285 +/- 341 dyn.s.cm-5.m-2 RsaI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Septic shock: a goal-directed therapy using volume loading, dobutamine and/or norepinephrine

In patients with septic shock and acute respiratory failure, norepinephrine (NE) alone or in combination with dobutamine was used. The aim of therapy was to obtain or maintain Cl greater than or equal to 4.5 l.min-1.m-2, SVR greater than or equal to 700-800 dyn.s.cm-5 and oxygen delivery (Do2) greater than or equal to 550 ml.min-1.m-2. Twenty-three patients (58 +/- 3 years) were studied. Initially patients were given intravenous fluid resuscitation to obtain optimal cardiac filling pressures. Eleven patients were considered to be in hyperdynamic septic shock (cardiac index (CI) greater than 4.5 l.min-1.m-2, SVR less than or equal to 600 dyn.s.cm-5 and oliguria) and were given NE as a single agent (0.9 +/- 0.2 micrograms kg-1.min-1). The other 12 patients had Cl less than 3.5 l.min-1.m-2 and were given a combination of dobutamine (12 +/- 0.09 micrograms.kg-1.min-1) and NE (1.1 +/- 0.2 micrograms.kg-1.min-1). The latter drug was added since systemic vascular resistance (SVR) was less than 600 and oliguria persisted while on dobutamine. In all patients, during NE infusion SVR was greater than 700 dyn.s.cm-5, Cl greater than or equal to 4.5 l.min-1.m-2 and Do2 greater than 550 ml.min-1.m-2. Urine flow was significantly increased during NE infusion, and only four patients remained oliguric. Anion gap and oxygen consumption were not modified. A complete resolution of septic shock was seen in 16 out of 23 patients (70%). Hospital mortality was 56%.     

Changes in ventilation, oxygen uptake, and carbon dioxide output during recovery from isoflurane anesthesia

Recovery from inhalation anesthesia is often marked by the occurrence of postoperative tremor that resembles shivering, which is known to be associated with an increase in oxygen uptake (VO2), CO2 output (VCO2), and minute ventilation (VE). This study determined the time course of the ventilatory changes observed during the first hour of recovery from isoflurane anesthesia. Ten patients (ASA PS 1) scheduled for minor orthopedic surgery (knee arthroscopy) were included in this study. Anesthesia was induced with thiopental (5 mg/kg) and maintained with 70% N2O and isoflurane (1-2%) in oxygen, allowing spontaneous ventilation. In the recovery room, after N2O had been discontinued, patients were connected to a Beckman Metabolic measurement cart, which allowed a continuous monitoring of VE, VO2, VCO2, and PETCO2. Postoperative tremor was observed in all patients within 7.1 +/- 1.2 min (mean +/- SEM) after isoflurane discontinuation and was associated with a marked increase in the following: VO2, from 173 +/- 26 ml/min at the end of anesthesia to 457 +/- 88 ml/min; VCO2, from 149 +/- 18 ml/min at the end of anesthesia to 573 +/- 98 ml/min; and VE, from 6.8 +/- 0.7 l/min at the end of anesthesia to 16.6 +/- 2.8 l/min (values obtained 20 min after isoflurane discontinuation). In three patients during intense shivering, VO2, VCO2, and VE reached peak values higher than 800 ml/min, 1,300 ml/min and 30 l/min, respectively. This study shows that postoperative tremor following isoflurane anesthesia may be associated with prolonged and large increases in oxygen uptake, CO2 output, and minute ventilation.     

Isoflurane and total oxygen consumption in spontaneously breathing dogs in basal metabolic conditions

To study the metabolic effects of isoflurane, whole body oxygen consumption (VO2) was measured on 7 occasions in 7 dogs under standard conditions. The dogs were trained to lie unrestrained in the lateral position for the measurement of VO2 (STPD) in the unanaesthetized state. Blood gas tensions and pH of arterial blood, heart and respiratory rates, blood pressure, rectal temperature and CO2 production (VCO2) also were determined. The maximum VO2 (ml X kg-1 X min-1) of the alert and the minimum of the drowsy resting states averaged (+/- SE) 6.9 +/- 0.5 and 3.6 +/- 0.3 respectively. The calculated mean basal rate was 4.4 +/- 0.1 and VO2 during natural delta-sleep 2.8 +/- 0.3. With isoflurane and spontaneous ventilation VO2 averaged 4.1 +/- 0.2, 4.0 +/- 0.3 and 3.6 +/- 0.3 at 1, 1.5 and 2 Vol-% (inspired) respectively. During anaesthesia with isoflurane VO2 fluctuates between the calculated basal rate and that of natural sleep.     

以氧供为导向的血流动力学管理模式对肝移植患者氧代谢及预后的影响

目的探讨在不同氧供(DO_2)水平的血流动力学管理模式下,不同程度肝功能损害患者非转流经典原位肝移植手术过程中机体氧代谢变化及其对患者预后的影响。方法选择接受经典非转流肝移植术患者70例,男48例,女22例,年龄37~66岁,ASAⅢ或Ⅳ级,随机分为对照组和研究组,每组35例。对照组为常规血流动力学管理组,维持术中DO_2在350~500ml·min-1·m~(-2);研究组以DO_2为导向血流动力学管理组,维持术中DO_2≥500ml·min~(-1)·m~(-2)。左桡动脉置管后常规麻醉诱导,经右颈内静脉放置Swan-Ganz导管连续监测心排指数(CI)和混合静脉血氧饱和度(S珔vO2)。分别于麻醉后手术前(T_1)、无肝期前10min(T_2)、无肝期30min(T_3)、新肝期30min(T_4)及术毕(T_5)抽取桡动脉血样做血气分析,记录动脉血氧饱和度(SaO_2)、PaO2和Hb,并计算DO_2、氧耗(VO2)及氧摄取率(ERO2)。术后记录ICU驻留时间和住院时间,出院后电话回访患者生存情况并应用健康检查简表SF-36问卷调查肝移植患者生存质量。结果与T_1时比较,T_3时两组患者CI、DO_2和VO_2均明显降低(P0.05);T_1~T_5时研究组患者CI、DO_2、VO_2明显高于对照组,ERO2明显低于对照组(P0.05)。术后研究组患者ICU驻留时间和总住院时间明显短于对照组(P0.05)。研究组患者生存质量参数评分和术后1~5年生存率高于对照组,但差异无统计学意义。结论以DO_2为导向的血流动力学管理模式,对不同程度肝功能损害患者肝移植术中机体氧代谢改善具有显著意义,DO_2的增加和氧代谢改善可有效缩短患者ICU驻留时间和总住院时间,患者生存质量有增加的趋势。     

Etomidate modifies hemodynamic response to fentanyl in patients with impaired left ventricular function]

The haemodynamic effects and the side-effects of anaesthesia using high doses of fentanyl were compared in two groups of 12 patients each. All the patients had poor left ventricular function and were scheduled for elective coronary artery bypass graft surgery or valvular replacement. Patients were randomly assigned to either group. In group EF, patients were given 5 micrograms.kg-1 of fentanyl, followed by 0.3 mg.kg-1 of etomidate. Once they had lost consciousness, they were given 15 mg of pancuronium and 25 micrograms.kg-1 of fentanyl over a 5 min period. Patients in group F received the full 30 micrograms.kg-1 dose of fentanyl over a 5 min period, followed by 15 mg of pancuronium. The patients were intubated 2 min after the end of the fentanyl infusion. They were mechanically ventilated with 100% oxygen. Anaesthesia was maintained with a continuous infusion of fentanyl (total dose 100 micrograms.kg-1). The usual haemodynamic parameters were monitored and calculated, as well as pain during injection of the drugs, myoclonia, chest wall rigidity and the time to loss of consciousness. The two groups were comparable with respect to age, weight, height and surgery. One third of the patients in group EF complained of pain during etomidate injection. The time required to loose consciousness was shorter in group EF (55 +/- 16 sec) than in group F (177 +/- 56 sec) (p < 0.001). The cardiac index decrease in group EF (2.0 +/- 0.4 l.min-1.m-2 vs. 1.9 +/- 0.4 l.min-1.m-2) (p < 0.05), respectively between the time just before tracheal intubation (T1), and 10 min after tracheal intubation (T3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperkinetic shock and cerebral malaria

Two cases of cerebral malaria with hyperkinetic shock are reported. The first case concerned a 39-year-old european male who was not taking any prophylactic anti-malarial drugs. After having had headache and fever for a week, he was admitted to the intensive care unit (ICU) in coma and with jaundice. His initial systolic blood pressure was 60 mmg, with a central venous pressure (CVP) of -3 cmH2O. Five-hundred ml of modified fluid gelatin increased the CVP without raising the blood pressure. Haemodynamic investigations revealed a cardiac index (CI) = 5.2 l.min-1.m-2, peripheral arterial resistances (Rsa) = 290 dyn.s.cm-5, oxygen consumption (VO2) = 120 ml.min-1.m-2. Despite treatment with dopamine and dobutamine, the patient died 3 h after his admission, with a CI of 1.9 l.min-1.m-2. The second patient was a 14-year-old senegalese girl, admitted in circumstances similar to the first case. Initial haemodynamic investigations gave the following figures: CI 6.5 l.min-1.m-2, Rsa = 476 dyn.s.cm-5, VO2 = 174 ml.min-1.m-2. Recovery was obtained with fluid replacement therapy and dopamine. In the absence of another associated infectious disease, the plasmodial origin of the septic shock would seem to be the most likely in both cases. Pathophysiological mechanisms of these algid forms of malaria remain enigmatic. Various factors are discussed: cytoadherence of erythrocytes infected with Plasmodium falciparum, immunological disturbances, or a specific endotoxin.     

Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance

To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean +/- SEM, 54 +/- 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU X m-2 X min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng X kg-1 X min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 +/- 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 +/- 8 versus 170 +/- 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 +/- 0.36 mg X kg-1 X min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 +/- 0.31 mg X kg-1 X min-1, P less than 0.02). Mean glucose clearance was also diminished with glucagon (4.49 +/- 0.32 versus 5.73 +/- 0.45 ml X kg-1 X min-1 preglucagon, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

CBF and CMRO2 during Continuous Etomidate Infusion Supplemented with N2O and Fentanyl in Patients with Supratentorial Cerebral Tumour. A Dose-Response Study

In 14 patients with supratentorial cerebral tumours with midline shift below 10 mm, CBF and CMRO2 were measured (Kety & Schmidt) during craniotomy. The anaesthesia was continuous etomidate infusion supplemented with nitrous oxide and fentanyl. The patients were divided into two groups. In Group 1 etomidate infusion of 30 micrograms kg-1 min-1 was used throughout the anaesthesia, and CBF and CMRO2 were measured twice. In this group CMRO2 (means +/- s.d.) averaged 2.31 +/- 0.43 ml O2 100 g-1 min-1 70 min after induction and 2.21 +/- 0.38 ml O2 100 g-1 min-1 130 min after induction. In Group 2 the etomidate infusion was increased from 30 to 60 micrograms kg-1 min-1 after the first study and a significant fall in CMRO2 from 2.52 +/- 0.56 to 1.76 +/- 0.40 ml O2 100 g-1 min-1 was found. Simultaneously, a significant fall in CBF was observed. The CO2 reactivity was preserved during anaesthesia.     

Exercise-induced fall in insulin and increase in fat metabolism during prolonged muscular work

The role of the exercise-induced fall in insulin in fat metabolism was studied in dogs during 150 min of treadmill exercise alone (controls) or with insulin clamped at basal levels by an intraportal infusion to prevent the normal fall in insulin concentration (ICs). To counteract the suppressive effect of insulin on glucagon release, glucagon was supplemented by an intraportal infusion in ICs. In all dogs, catheters were placed in a carotid artery and in the portal and hepatic veins for sampling and in the vena cava and the splenic vein for infusion purposes. Glucose levels were clamped in ICs to recreate the glycemic response evident in controls. In controls, insulin fell by 7 +/- 1 microU/ml but was unchanged from basal levels in ICs (0 +/- 2 microU/ml). Glucagon, norepinephrine, epinephrine, and cortisol rose similarly in controls and ICs. Arterial free-fatty acid (FFA) levels rose by 644 +/- 126 mu eq/L in controls but did not increase in ICs (-12 +/- 148 mu eq/L). Arterial glycerol levels rose by 337 +/- 43 and 183 +/- 19 microM in controls and ICs. Hepatic FFA delivery and fractional extraction increased by 17 +/- 3 and 0.06 +/- 0.02 mumol.kg-1.min-1, respectively, in controls. In ICs, hepatic FFA delivery increased by only 1 +/- 2 mumol.kg-1.min-1, whereas hepatic fractional extraction fell slightly (-0.03 +/- 0.03). Consequently, net hepatic FFA uptake rose by 4.8 +/- 1.5 mumol.kg-1.min-1 in controls but decreased slightly in ICs (-0.5 +/- 1.1 mumol.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

The pharmacokinetics of midazolam in chronic renal failure patients

Fifteen patients with chronic renal failure (CRF) were given midazolam 0.2 mg/kg iv over 15 s. All but one lost consciousness in a time ranging from 22-100 s (mean +/- SD was 55 +/- 26 s) after drug administration. Patients regained consciousness from 6-105 min (mean 53 +/- 32) after drug administration. The calculated mean plasma level of midazolam at arousal was 81 +/- 47 ng/ml. Pharmacokinetics parameters were determined from midazolam plasma levels measured in 16 consecutive venous blood samples. The pharmacokinetic parameters in CRF patients were compared with those of healthy volunteers matched for age, sex, and body size with the CRF patients. Protein binding was determined by equilibrium dialysis. CRF patients had a significantly higher (P less than 0.005) plasma-free drug fraction (6.5% +/- 0.7) compared with the control patients (3.9% +/- 0.1). Total (bound plus unbound) kinetics differed in the two groups: volume of distribution 3.8 +/- .3 1/kg in CRF patients versus 2.2 +/- .2 1/kg in controls (P less than 0.001), and clearance 11.4 +/- 1.6 ml X min-1 X kg-1 in CRF patients versus 6.7 +/- 0.9 ml X min-1 X kg-1 in controls (P less than 0.02). When kinetic parameters were corrected for protein binding, CRF patients unbound volume of distribution (63.5 +/- 6.8 1/kg) and free drug clearance (189 +/- 29 ml X min-1 X kg-1) were not different from the control group's volume of distribution (55.6 +/- 5.7 1/kg) and free drug clearance (176 +/- 24 ml X min-1 X kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration.

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)     

Changes in pulmonary function test and cardio-pulmonary exercise capacity in COPD patients after lobar pulmonary resection.

OBJECTIVE: Pulmonary Function Tests (PFT) and Cardio-Pulmonary Exercise Testing (C-PET) are useful to evaluate operability in functionally compromised patients. Although modifications of PFT and C-PET after lung surgery have been widely explored, little information exists as to modifications of exercise capacity in COPD patients undergoing lung resection. We prospectively analyzed the changes in PFT and C-PET in patients with COPD after a pulmonary lobar resection. METHODS: From January 2003 to March 2004 all patients scheduled for lung resection were considered for participation in the study protocol. Those patients with a preoperative diagnosis of COPD on PFT were explored through a C-PET. Only patients who had undergone a lobar pulmonary resection were subsequently considered; these patients had a new complete cardio-respiratory evaluation 3 months after surgery. The pre- and postoperative values compared were those of FEV1, TLC, DLCO, VO2max, and VE/VCO2. Data are expressed as mean +/- standard deviation (SD). Statistic evaluation was made using the Wilcoxon test. RESULTS: During this period 11 patients completed the study protocol. Ten patients underwent surgery for NSCLC and one for a pulmonary aspergilloma. Nine lobectomies and two bilobectomies were performed. In the study population, the preoperative mean value of FEV1 resulted as being 53% (SD+/-20) of the predicted mean value, that of TLC 120% (SD+/-35) and that of DLCO 65% (SD+/-27). The preoperative mean value of VO2max resulted as being 17.8 ml/Kg/min (SD+/-3.25) and mean VE/VCO2 resulted as being 35.7 (SD+/-4). Three months after surgery the measured mean value of FEV1 was 53% (SD+/-18), that of TLC was 99% (SD+/-24) and that of DLCO 52% (SD+/-18). The mean value of VO2max resulted as being 14.1 ml/Kg/min (SD+/-3.04) and that of VE/VCO2 was 42.5 (SD+/-12.8). Statistical analysis of PFT values showed that FEV1 and DLCO were not significantly modified (P > 0.05); in contrast, TLC had significantly decreased (P = 0.008). VO2max had significantly decreased (P = 0.004) and VE/VCO2 had significantly increased (P = 0.018). CONCLUSIONS: Three months after a lobar pulmonary resection, patients with COPD were found to have a significant decrease in exercise tolerance. PFT alone can underestimate the postoperative loss of exercise capacity through exercise.     

Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients.

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)