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%.     

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.     

Thiopental attenuates relaxation and cyclic GMP production in vascular smooth muscle of endotoxin-treated rat aorta, independent of nitric oxide production

As thiopental (thiopentone) suppresses cyclic GMP (cGMP) formation produced by nitric oxide donor drugs, we have tested if it suppresses cGMP formation and increases vascular tone after induction of calcium- calmodulin-independent nitric oxide synthase (iNOS). Rat aortic rings were treated with Escherichia coli lipopolysaccharide (LPS) 1 microgram ml-1 for 4 h, and the effects of thiopental on tension, cGMP concentrations and nitrite accumulation were determined. Thiopental 0.3 mmol litre-1 reduced the tension of phenylephrine-precontracted aortic rings before LPS treatment, but caused no significant effects on tension in the presence of L-arginine 10 microgramsmol litre-1 after LPS treatment. L-Arginine 1 microgramsmol litre-1 to 1 mmol litre-1 increased concentrations of cGMP in LPS-treated aorta in a concentration- dependent manner. This was reduced by thiopental 0.3-1 mmol litre-1. Treatment with L-arginine 1 mmol litre-1 increased concentrations of nitrite, the end product of nitric oxide; this was not affected by thiopental 1 mmol litre-1. We conclude that thiopental suppressed cGMP formation in iNOS-induced vascular smooth muscle without affecting nitric oxide production.      

The cytokines IL-1beta and IL-1 receptor antagonist, IL-2 and IL-2 soluble receptor-alpha, IL-6 and IL-6 soluble receptor, TNF-alpha and TNF soluble receptor I, and IL10 in drained and systemic blood after major orthopaedic surgery.

OBJECTIVE: To measure the concentration of the cytokines interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumour necrosis factor-alpha (TNF-alpha) and the modulators of their function interleukin-1 receptor antagonist (IL-1Ra), interleukin-2 soluble receptor alpha (IL-2 sRalpha), interleukin-6 soluble receptor (IL-6sR) and soluble tumour necrosis factor receptor I (sTNFR-I) in systemic and drained blood for the first six hours after a major orthopaedic operation. DESIGN: Prospective study. SETTING: University hospital, Oslo. PATIENTS: 8 patients operated on for thoracic scoliosis. MAIN OUTCOME MEASURE: Concentrations of IL-1beta, IL-2, IL-6, IL-10, TNF-alpha, IL-1Ra, IL-2 sRalpha , IL-6sR, and sTNFR-I were measured together with haemoglobin (Hb) concentration, white cell count (WCC), and differential count in arterial and drained blood at wound closure and 1, 2, 4, and 6 hours postoperatively. RESULTS: IL-1beta and IL-6 concentrations increased significantly in drained blood, whereas that of TNF-alpha increased only in arterial blood. The modulating factors IL-1Ra, sTNFR-I, and IL-10 were increased both in arterial and drained blood. IL-6sR had decreased slightly at 6 hours in drained blood. No IL-2 was found and IL-2 sRalpha decreased simultaneously with the haemodilution. In arterial blood there was a granulocytosis and in drained blood a relative lymphocytosis. CONCLUSION: Cytokine responses to surgical trauma include modulating factors such as soluble receptors and receptor antagonists that have different responses systemically and locally.     

Modifications hemodynamiques durant la cœlioscopie: étude menée par bioimpédance électrique thoracique

In 18 women A.S.A. physical status 1, a noninvasive thoracic electrical bioimpedance method was used to evaluate haemodynamic changes during gynaecological laparoscopy. A significant decrease in cardiac index was observed after peritoneal insufflation, from 3.2 to 2.8 L.min-1.m-2 and returned to the initial values after ten minutes of Trendelenburg's position. Elevated intra-abdominal pressure was also associated with a significant increase in mean arterial pressure (from 68 to 88 mmHg) and systemic vascular resistance index (from 1620 to 2491 dyn.s.cm-5.m-2). However, values were not restored after peritoneal exsufflation: systemic vascular resistance index values remained 30 per cent higher than that before insufflation. Decreased venous return may account for the significant decrease in cardiac output but mechanical compression does not explain the persistent elevation of systemic vascular resistance.     

Circulatory and respiratory effects of celioscopy in the obese

Hemodynamic and respiratory variations were measured in ten obese women scheduled for laparoscopy. Peritoneal insufflation was associated with a decreased cardiac index (from 2.80 to 2.26 1 X min-1 X m-2; p less than 0.01) and increased systemic vascular resistances (from 1,230 to 1,940 dyn X s X cm-5). Heart rate remained stable (from 85 to 86 c X min-1). Mean arterial pressure was increased (from 86 to 104 mmHg; p less than 0.01). Placing the patients in Trendelenburg's position was associated with a small increase in cardiac index (from 2.26 to 2.49 l X min-1 X m-2; p less than 0.05). Under controlled ventilation, Paco2 was slightly increased (from 26 to 30 mmHg; p less than 0.01). A decrease in venous return due to intraperitoneal vascular compression explained the decrease in cardiac output. The rise in PaCO2 could be explained by CO2 reabsorption from the peritoneal cavity, and also by a change in the ventilation/perfusion ratio due to the curarization, mechanical ventilation and increased abdominal pressure. These results did not differ from the data available in non obese patients.     

Hemodynamic effects of a continuous infusion of levosimendan in critically ill patients with cardiogenic shock requiring catecholamines

BACKGROUND: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in desperately ill patients with cardiogenic shock requiring catecholamines. METHODS: Ten patients with cardiogenic shock received levosimendan as continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. The patients were otherwise unselected. Hemodynamic measurements were routinely performed at baseline (time 0) and at 1, 8, 16 and 24 h after start of levosimendan (LS) using a Swan-Ganz thermodilution catheter. RESULTS: During the levosimendan infusion there was a significant increase in cardiac index from 1.8 +/- 0.4 to 2.4 +/- 0.6 L*min-1*m-2 (P = 0.023) and a significant decrease in systemic vascular resistance from 1559 +/- 430 to 1109 +/- 202 dyn*s*cm-5 (P = 0.001), respectively. Changes in catecholamine dose, and in systolic and diastolic blood pressure were not significant. Given the individual response to LS, 8/10 patients showed an increase in left ventricular stroke work index under reduced or roughly unchanged preload conditions after 8 h. CONCLUSION: This series shows that a LS infusion is feasible and able to improve hemodynamics in severely compromized, critically ill patients with cardiogenic shock requiring catecholamine therapy. Its potential advantages when compared with other inotropes are unclear. To clarify the potential role of LS in this clinical setting randomized controlled trials on hemodynamic and mortality endpoints are needed.     

Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass

Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations

To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment.     

Cardiovascular effects of apnea test in the diagnosis of brain death

Cardiovascular effects of apnea test were investigated in 12 patients suspected of brain death. Arterial blood gas and cardiovascular hemodynamics were measured just before and after 10-minute apnea. Apnea test induced respiratory acidosis without hypoxemia. Cardiac index increased by 34% (2.3 to 3.1 l.min-1.m-2; P less than 0.01) and systemic vascular resistance index decreased by 30% (3608 to 2519 dynes.sec.cm-5.m-2; P less than 0.01), whereas heart rate and mean arterial pressure were unchanged. Significant increases in mean pulmonary arterial pressure (17.6 to 29.1 mmHg; P less than 0.01), pulmonary vascular resistance index (381 to 616 dynes.sec.cm-5.m-2; P less than 0.01) and right ventricular stroke work index (4.0 to 10.5 g.m.m-2; P less than 0.01) suggest that apnea test increases right ventricular afterload.     

Haemodynamic measurements (continuous cardiac output and systemic vascular resistance) in critically ill patients: transoesophageal Doppler versus continuous thermodilution

Ten critically ill patients underwent this prospective study to assess the reliability of the continuous thermodilution versus transoesophageal Doppler techniques in the determination of continuous cardiac output (CO) and systemic vascular resistance (SVR). A total of 145 pairs of CO and SVR measurements were obtained by both a pulmonary artery catheter with a heated filament and a transoesophageal Doppler apparatus (ODM II). Total CO ranged from 2.4 and 13 l.min-1; the bias of all measurements was 0.01 +/- 0.48 l.min-1, and the 95% confidence limits (mean difference +/- 2 SD) were 0.97/0.96 l.min-1. Total SVR ranged from 309 and 2643 dyn.s.cm-5; the bias of all measurements was 18 +/- 127 dyn.s.cm-5, and the 95%, confidence limits were 272/236 dyn.s.cm-5. Transoesophageal Doppler accurately measures continuous CO and SVR in critically ill patients. It should be viewed as complementary to pulmonary catheterization.     

Adrenaline: relationship between infusion rate, plasma concentration, metabolic and haemodynamic effects in volunteers.

The present study investigated the relationship between supraphysiological plasma concentrations of adrenaline and the resulting haemodynamic and metabolic effects. Adrenaline was administered at five infusion rates (0.01-0.2 micrograms kg-1 min-1) in an escalating sequence to eight volunteers. The arterial plasma concentration of adrenaline increased from 53 +/- 44 to 4349 +/- 818 ng litre-1 during the highest infusion rate. Typical haemodynamic responses, such as increase in blood pressure and heart rate, were seen. The plasma concentrations of glucose and lactate increased from 5.2 +/- 0.4 to 13.7 +/- 1.3 mmol litre-1 and from 0.9 +/- 0.3 to 4.7 +/- 2.6 mmol litre-1, respectively, during the highest infusion rate without a significant increase in insulin concentration. Non-esterified fatty acids increased from 379 +/- 97 to 1114 +/- 331 mumol litre-1 during the 0.06 microgram kg-1 min-1 infusion rate. Adrenaline had no selective haemodynamic effect. If similar metabolic effects occur in patients during treatment with adrenaline or other sympathomimetics, they may further increase breakdown of energy stores in a situation of increased catabolism, and impair utilization of parenteral nutrition.     

Effects of methylprednisolone on complement activation and leukocyte counts during cardiopulmonary bypass

Generation of the complement activation products C3dg and terminal complement complex (TCC) and numerical changes in peripheral granulocytes (PMN) and lymphocytes were assessed in patients undergoing aortocoronary bypass surgery with extracorporeal circulation (ECC). Fluid from bronchial lavage performed preoperatively and 4 hours postoperatively was analyzed for granulocyte elastase activity and PMN content. Ten of the 20 patients received methylprednisolone (30 mg/kg b.w.) immediately before ECC. No difference was found between them and the control group regarding C3dg and TCC, and both groups showed similar postoperative decrease of peripheral blood lymphocytes. The postoperative PMN count in peripheral blood was significantly higher in the methylprednisolone group than in the controls from 12 hours onwards. In bronchial lavage fluid the postoperative PMN count was unaltered in the methylprednisolone group, but significantly increased in the controls. No granulocyte elastase activity was found before or after surgery in either group. The results indicated that methylprednisolone does not affect complement activation during cardiopulmonary bypass, but increases the granulocytes in peripheral blood postoperatively.     

Vascular effects of urapidil administrated during extracorporeal circulation]

Urapidil exerts a combined central sympathetic and peripheral alpha-1 adrenergic receptor inhibition. Urapidil induces arterial vasodilation but its effects on venous capacitance are more difficult to assess. During cardiopulmonary bypass with constant perfusion index (2.4 l.min-1 x m-2) total peripheral resistance varies similarly as to arterial pressure and, as the apparatus venous reservoir is filled continuously by simple gravity from the right atrium, a decrease in venous blood reservoir level reflects an increased venous capacitance. Twenty-six patients undergoing cardiac surgery were anaesthetized with fentanyl and midazolam and randomly assigned to one of two groups. During normothermic cardiopulmonary bypass, group 1 was administered i.v. urapidil 12.5 mg and group 2 a placebo. In group 1, arterial pressure decreased by 33 +/- 14% (mean +/- SD) at the second minute while total peripheral resistance decreased from 1,384 +/- 255 to 927 +/- 193 dyn.s.cm-5. Then this two parameters regained group 2 values after the eighth minute. Reservoir blood level was lower in group 1 than in group 2 from the second to the eight minute (p < 0.05) with maximum effect at 7 minutes. It is concluded that urapidil exerts arterial and venous dilation. Its arterial effects seem greater during normothermic cardiopulmonary bypass than in normal conditions and its maximum venous effects seem to occur after its maximum arterial effects. The short duration of action may be due to the small dose administered.     

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)     

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)     

Granulocytes in bronchial lavage fluid after major vascular surgery

Increased numbers of polymorphonuclear granulocytes (PMN) in the airways, as measured by PMN content in bronchial lavage fluid (P less than 0.01), were found 3 h postoperatively in ten patients undergoing surgery for lumbar aortic aneurysms. An increase in plasma levels of the complement split product C3dg from 6 (0-19) AU/ml preoperatively to 20 (13-50) AU/ml 3 h after surgery (P less than 0.01), indicates an activation of the complement cascade. These changes were not accompanied by increased elastase activity in the bronchial lavage fluid or by major changes in pulmonary blood gas exchange or vascular resistance, indicating that massive PMN activation, analogous to that proposed in adult respiratory distress syndrome (ARDS) had not taken place. In conclusion, complement system activation and migration of PMN into the airways, as seen in connection with major vascular surgery, does not seem to contribute to ARDS-type pulmonary dysfunction.     

Patient-maintained propofol sedation as premedication in day-case surgery: assessment of a target-controlled system

We have assessed the efficacy and safety of a system which allowed 20 patients undergoing day-case anaesthesia to operate a target-controlled infusion of propofol to provide anxiolytic premedication. A target- controlled infusion of propofol was started with a target blood concentration of 1 microgram ml-1, and the patient was allowed to increase the target by 0.2 microgram ml-1 by operating a control button. There was a lockout time of 2 min and a maximum target concentration of 3 micrograms ml-1. There were significant reductions in anxiety scores from presedation baseline values and those measured at 15 min after the start of sedation. Values remained low until induction of anaesthesia. Median blood target concentration of propofol varied from 1.0 to 1.2 micrograms ml-1 and mean propofol consumption was 50.3 (SD 17.6) micrograms kg-1 min-1. No patient became oversedated and all remained cardiovascularly stable. Two individuals required low- dose supplementary oxygen for mild arterial oxygen desaturation but there were no instances of airway obstruction. Patient satisfaction with the system was high.      

Endocrine and metabolic effects of hypotension or halothane inhalation in sheep anaesthetized with pentobarbital

We have studied the mechanism whereby halothane induces adrenocortical activity in eight sheep anaesthetized twice for 2 h with pentobarbital. During the second hour they received infusion of nitroprusside to lower mean arterial pressure by 40 mm Hg (group NP) or on another occasion they inhaled 0.5% halothane (group HAL). Plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate were measured. Infusion of nitroprusside increased cortisol concentrations from mean 44 (SD 33) to 256 (131) nmol litre-1 (P < 0.05), AVP from 19 (14) to 174 (102) pmol litre-1 (P < 0.05) and ACTH from 30 (17) to 54 (32) pmol litre-1. Glucose and lactate concentrations did not change significantly. After 60 min of halothane administration, there were fewer effects: plasma cortisol increased from 47 (39) to 63 (44) nmol litre-1 (P > 0.05) and AVP from 14 (11) to 32 (29) pmol litre-1 (P > 0.05) while ACTH decreased from 32 (13) to 25 (10) pmol litre-1. The AUC60-120 values for all three hormones were significantly lower in group HAL than in group NP (P < 0.01). Glucose was unchanged but lactate concentration decreased. These results support, but do not prove, the hypothesis that hypotension is the main stimulus to pituitary-adrenocortical activity during halothane anaesthesia in sheep. A direct effect of nitroprusside cannot be ruled out.      

Cerebrospinal fluid concentrations of propofol during anaesthesia in humans

The concentration of propofol in and surrounding the human brain during propofol anaesthesia is unknown. We measured simultaneously the concentration of propofol in cerebrospinal fluid (CSF) from an indwelling intraventricular catheter and the concentration in arterial blood in five neurosurgical patients before, during induction (at 2.5 and 5 min) and during a maintenance propofol infusion (at 15 and 30 min). After induction of anaesthesia with propofol 2 mg kg-1, anaesthesia was maintained with an infusion of 8 mg kg-1 h-1 for 15 min and then reduced to 6 mg kg-1 h-1. The plasma concentration of propofol increased rapidly during induction and reached a plateau concentration of mean 2.24 (SD 0.66) micrograms ml-1 after 5 min. The concentration of propofol in CSF showed a slower increase during induction and remained almost constant at 35.5 (19.6) ng ml-1 at 15-30 min after induction. The CSF concentration of propofol that we measured was 1.6% of the plasma concentration and consistent with the high protein binding of the drug in plasma.