A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients.

STUDY OBJECTIVE: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. DESIGN: Phase III, randomized, open-label clinical trial. SETTING: 12 international surgical units. PATIENTS: 555 consenting inpatients undergoing surgeries of intermediate duration. INTERVENTIONS: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N2O) (up to 70%) and oxygen (O2) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variable was permitted. Comparison of efficacy was based on observations made of the rapidly and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia in the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients 171 both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 +/- 0.6, 12.8 +/- 0.7, 17.2 +/- 0.9, 46.1 +/- 3.0 minutes, respectively, versus isoflurane, 16.4 +/- 0.6, 18.4 +/- 0.7, 24.7 +/- 0.9, 55.4 +/- 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients on the sevoflurane group had no untoward effect versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 microM/I. or greater though standard tests indicated no evidence of associated renal dysfunction. CONCLUSION: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recover.

Enhanced pneumonia resolution by inhalation of nitric oxide?

We present a patient with severe bacteraemic pneumococcal pneumonia associated with severe hypoxaemia, where nitric oxide (NO) 15-40 ppm was added to the inspired gas. Nitric oxide therapy improved gas exchange, reduced pulmonary vasoconstriction and peak airway pressure. The patient survived. We observed an unexpected rapid and complete disappearance of bilateral pulmonary infiltrates during the first 120 h of the 7-day NO inhalation period.

Opioid supplementation to propofol anaesthesia for outpatient abortion: a comparison between alfentanil, fentanyl and placebo.

One hundred and sixty-four patients scheduled for elective termination of pregnancy under general anaesthesia were randomly assigned to receive one of three different supplements to propofol and oxygen in nitrous oxide anaesthesia: 0.1 mg fentanyl, 0.5 mg alfentanil or placebo. Postoperative pain and nausea, as well as complications during anaesthesia were studied. There were no differences in complications or complaints by surgeons during anaesthesia, and no patient in any group reacted unsatisfactorily to surgery. The patients in the placebo group consumed significantly more propofol during the procedure (P less than 0.001). No differences were seen in time until hospital discharge between the three groups. Complaints about postoperative pain were significantly less frequent among patients receiving fentanyl (P less than 0.01). The number of patients requesting postoperative analgetics, however, did not differ. There was no difference in the frequency of nausea or vomiting, but postoperative pain was found significantly to increase complaints of nausea (P less than 0.01) and also time until hospital discharge (P less than 0.01). In conclusion, opioid supplementation lowered the amount of propofol needed for anaesthesia. Alfentanil 0.5 mg did not improve the postoperative course. Fentanyl 0.1 mg decreased the frequency of postoperative pain without increasing the time to hospital discharge.

Plasma substitution with 3% dextran-60 in orthopaedic surgery: influence on plasma colloid osmotic pressure, coagulation parameters, immunoglobulins and other plasma constituents.

To study the effects on plasma proteins, blood coagulation and fibrinolysis of dextran-60, given as plasma volume substitute in a 3% solution, 57 patients were studied preoperatively and for 8 days postoperatively in conjunction with elective orthopaedic surgery. Three groups were formed according to the blood loss during the day of surgery: Group I (n = 22) less than 30%, Group II (n = 24) 30-50% and Group III (n = 11) greater than 50% of the estimated blood volume. Dilution to a haemoglobin concentration of 110 g.1-1 was intended and erythrocytes transfused accordingly. No platelets were transfused. All patients received similar amounts of crystalloids. Nine patients in Group III received plasma and/or albumin solution for further volume replacement once the maximum dose of dextran (1.5 g.kg-1) was reached. Dextran-70 was given on days 1 and 3 postoperatively for thromboprophylaxis. No patient exhibited clinical signs of thrombosis or embolism. Mean postoperative bleeding times were longer than preoperatively, but still within the normal range in all groups. They were both pre- and postoperatively slightly longer in Group III, compared to the other groups, perhaps due to mild haemostatic disorders and/or undisclosed antiphlogistic therapy. Postoperative colloid osmotic pressures decreased by 11-19% in the three groups. Dilution of plasma constituents was also seen in the postoperative fall of platelet counts and of albumin, antithrombin and Factor X levels, most marked in Group III. Albumin levels on day 8 were still only 77-83% of preoperative values. IgG and IgM were decreased and the IgG level was still only 75% of preoperative on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Discomfort after outpatient abortion using paracervical block: a comparison between two opioids and one non-opioid drug for premedication.

One hundred and one patients undergoing outpatient abortion using local anesthesia were randomly allocated to one of three different premedications: morphine-scopolamine, pethidine or midazolam. The incidence of pain, anxiety, emetic (nausea-vomiting) and patient cooperation was analyzed. Discomfort was frequently noticed, 79 patients reported pain, 57 nausea and 26 vomited at least once during the postoperative period which lasted 2.6 h (mean value). There were no major differences in complaints among the different premedication groups. Nausea, though, was correlated to pain. Symptoms of pain, nausea and vomiting were frequent after abortion under paracervical block. These complaints were not found to be related to the type of premedication or other circumstances in the perioperative period.

PIP: To contribute to the debate regarding the use of premedication before brief surgical procedures, 101 women undergoing outpatient abortion under local anesthesia were randomly assigned to receive morphine- scopolamine, pethidine, or midazolam. The perioperative course was evaluated by the gynecologist, nursing staff, and abortion patients in terms of cooperation, anxiety level, and discomfort. During the observation period (mean time of 2.6 hours), 59 women reported pain, 55 were nauseous, and 26 vomited at least once. Although there was no association between the type of premedication received and postoperative symptoms, the women in the morphine-scopolamine group required a significantly longer stay (mean of 2.9 hours) in the recovery room. Pain, reported by 70% of the patients, was the only factor significantly associated with nausea and vomiting. In terms of anxiety, 52 women indicated they were calm throughout the procedure. There was no difference between midazolam and the 2 opioids in the level of anxiety.

Activation of cascade systems by hip arthroplasty. No difference between fixation with and without cement.

The acrylic bone cement has been regarded as a very potent activator of the hemostatic mechanisms. A battery of coagulation, fibrinolytic, and kallikrein variables were studied perioperatively in 21 patients undergoing hip arthroplasty with fixation of the prosthesis either with (Charnley) or without (HP-Garches) cement. Epidural analgesia was used and dextran 6 per cent as thromboprophylaxis. The HP-Garches procedure was shorter and caused less blood loss. No differences were found between the two surgical procedures regarding the activation of the cascade systems. The coagulation and fibrinolytic systems were activated early, but a week postoperatively the latter seems to predominate. A marked activation of the kallikrein system was apparent. Our study shows that despite thromboprophylaxis a marked activation of the coagulation, fibrinolytic, and kallikrein systems occurs in relation to hip arthroplasty irrespective of the use or nonuse of cement and irrespective of the volume of blood loss during surgery. It may be the reaming of the bone marrow that initiates the activation of the cascade systems.

Effects of prenalterol and volume loading with dextran on haemodynamics and oxygen consumption in dogs during high epidural block with special reference to the splanchnic region.

High lumbar epidural block was induced in seven dogs, causing a fall in mean arterial blood pressure (AP) from 24.5 +/- 2.9 to 12.0 +/- 3.1 kPa owing to reductions in cardiac output (QT) and systemic vascular resistance (SVR) to 67% and 68% of the pre-epidural values. Volume loading with dextran 10 ml X kg-1 b.w. increased QT nearly to the pre-epidural value. SVR decreased further to 61% of the pre-epidural value and AP was only slightly increased to 14.9 +/- 2.7 kPa. Subsequent administration of prenalterol 20 micrograms X kg-1 b.w. caused a further increase in QT to 17% above the pre-epidural value due to an increase in heart rate of 51 beats/min. AP did not change since SVR decreased further to 49% of the pre-epidural value. The hepatic arterial blood flow (QHA) was essentially unchanged during epidural block as well as during volume loading, while the portal venous blood flow (Qpv) was changed concurrently with (QT). In spite of the decrease in SVR, the preportal and hepatic arterial vascular resistances were not diminished following prenalterol. The increase in OT must therefore have favoured other vascular beds. Hepatic and pre-portal tissue oxygen uptakes were unchanged during the experimental procedure, while whole-body oxygen uptake decreased by 20% following the epidural block and increased nearly to the pre-epidural level following volume loading in combination with prenalterol.

Renin release during controlled hypotension with sodium nitroprusside, nitroglycerin and adenosine: a comparative study in the dog.

The haemodynamic effects of i.v. infusions of sodium nitroprusside (SNP), nitroglycerin (TNG), and adenosine were studied in dogs in parallel with quantitative determinations of plasma renin activity (PRA) by radioimmunoassay. The drugs were given for controlled hypotension, and the mean arterial blood pressure (MABP) was decreased to approximately 50 mmHg (6.7 kPa). Arterial blood samples for PRA were collected at 10-min intervals. During the last interval the dogs were subjected to haemorrhagic shock. SNP-induced hypotension could be maintained only with a stepwise increase in infusion rate, from 11.8 to 16.0 micrograms X kg-1 X min-1 (P less than 0.05). TNG could not produce the desired blood pressure level, but gradually increasing doses induced a gradually decreasing MABP (80-60 mmHg) (10.7-8.0 kPa). During adenosine-induced hypotension, a perfectly stable blood pressure level was maintained without dose adjustments. Both SNP and TNG induced blood pressure-dependent increases in PRA, while no changes in PRA were seen during adenosine-induced hypotension. Nor could haemorrhagic shock, which induced further increases in PRA during SNP- and TNG-induced hypotension, alter PRA during adenosine infusions. We conclude that adenosine differs markedly from conventional hypotensive drugs such as SNP and TNG with respect to stability of action and dose requirements, and that this stability is related to an inhibited increase in renin release.

Effects of ephedrine on haemodynamics and oxygen consumption in the dog during high epidural block with special reference to the splanchnic region.

High lumbar epidural block was induced in seven dogs with 0.5% bupivacaine, causing a fall in mean arterial blood pressure (AP) from 19.2 +/- 3.2 to 10.5 +/- 3.2 kPa, owing to equal reductions in cardiac output (QT) and systemic vascular resistance (SVR). After the administration of ephedrine (a single injection of 200-300 micrograms X kg-1 b.w. followed by a continuous infusion of 10-20 micrograms X kg-1 b.w. X min-1) AP, QT and SVR rose to pre-epidural values. Furthermore, the hypokinetic circulation following the epidural block returned to normokinetic levels. Portal venous blood flow was increased from 16.5 +/- 6.2 to 25.5 +/- 4.3 ml X kg-1 b.w. X min-1 by ephedrine, while the hepatic arterial blood flow was unchanged and remained at its pre-epidural level. In spite of a slight rise in hepatic oxygen consumption from 1.2 +/- 0.4 to 1.6 +/- 0.6 ml X kg-1 b.w. X min-1, the percentages of oxygen extracted from the portal vein and the hepatic artery decreased significantly. It is concluded that ephedrine restores central and splanchnic haemodynamics in a desirable manner during high epidural anaesthesia.

Central and splanchnic hemodynamics in the dog during controlled hypotension with adenosine.

Central and splanchnic hemodynamic effects during controlled hypotension induced by the administration of the endogenous vasodilator adenosine were studied in ten artificially ventilated dogs under neurolept anesthesia. Adenosine was administered as a continuous infusion in the aorta (n = 3), in the inferior vena cava (n = 3), and after pretreatment with dipyridamole (which inhibits the cellular uptake of adenosine) (n = 4) in a dose sufficient to maintain a mean arterial blood pressure (MABP) level of approximately 50 mmHg. Observations were made before and after 20 min of controlled hypotension. Basal arterial plasma levels of adenosine were in the 10(-7) M range (means = 0.4 microM). The hemodynamic response was similar in all three settings. Adenosine caused a profound decrease in systemic vascular resistance (SVR) (52%, P less than 0.01) and preportal vascular resistance (PPR) (64%, P less than 0.01), while hepatic arterial vascular resistance ( HAR ) increased by 49% (P less than 0.05). Cardiac output increased (22%, P less than 0.05) through increase of stroke volume (77%, P less than 0.01), while heart rate decreased (28%, P less than 0.01). Whole-body oxygen uptake decreased (14%, P less than 0.01). Portal venous blood flow increased by 28% (P less than 0.05), whereas hepatic arterial blood flow decreased by 70% (P less than 0.01). In the preportal tissues, oxygen uptake decreased by 21% (P less than 0.01). In contrast, hepatic oxygen consumption increased (53%, P less than 0.05). Adenosine-induced hypotension was not associated with changes in plasma renin activity or the plasma concentration of norepinephrine. It is concluded that adenosine causes a rapidly induced and easily maintained hypotension and may be a potentially useful agent for controlled hypotension in patients.

Central and splanchnic haemodynamics in the dog during controlled hypotension with sodium nitroprusside.

The effects of controlled hypotension induced by sodium nitroprusside (SNP) on central and splanchnic haemodynamics were studied in ten artificially ventilated dogs under neurolept anaesthesia. SNP was given intravenously as a continuous infusion in order to maintain a mean arterial blood pressure (MABP) of about 50 mmHg. Observations were made before (control) and at 20 and 60 min after the start of the SNP infusion. The mean SNP dosage was 13.7 micrograms X kg-1 X min-1. Systemic vascular resistance (SVR) decreased by 47%. After 20 min there was a 17% decrease in cardiac output, while the hepatic arterial blood flow was diminished by 39%, and portal venous blood flow by 16%. Cardiac output and portal venous blood flow tended to return towards control values at 60 min, while the hepatic arterial blood flow remained depressed. The total oxygen uptake was unaltered after 20 min, but slightly decreased after 60 min. There were no changes in hepatic or preportal tissue oxygen consumption, nor in hepatic lactate uptake. It is concluded that SNP-induced hypotension was achieved primarily by a profound reduction of SVR, and initially also by a slight decrease in cardiac output. Although splanchnic and hepatic blood flows decreased, there were no signs of hypoxia in the preportal tissues or in the liver.

Relationship between arterial and venous adenosine levels and vasodilatation during ATP- and adenosine-infusion in dogs.

The hemodynamic effects of ATP and adenosine (i.v. infusions) were studied in dogs in parallel with quantitative determination of purines in plasma by HPLC. In two experiments, infusion were performed during treatment with dipyridamole, an uptake inhibitor of adenosine. A 50-60% reduction of mean arterial blood pressure (MABP) was induced by both ATP and adenosine at infusion rates ranging between 17-290 mumoles/min. Cardiac output was unaffected by the purine infusions, indicating that the reduction of MABP was caused by a reduction of the systemic vascular resistance. Elevated ATP and adenosine concentrations were seen in venous plasma (pulmonary artery) during infusion, while only approximately 10% recovered ATP had been degraded to adenosine. On the other hand, in arterial plasma, virtually all nucleotides had been eliminated whereas the adenosine concentrations in plasma ranged between 5 and 20 microM. The magnitude of the vasodilatation was strictly related to the arterial plasma adenosine level irrespective of whether ATP or adenosine was infused. Thus, adenosine probably mediates the vasodilatory effect of ATP.

Effects of dihydroergotamine on haemodynamics and oxygen consumption in the dog during high epidural block with special reference to the splanchnic region.

Dihydroergotamine (DHE) 0.02 mg X kg-1 was administered i.v. in 9 dogs with high epidural block. Mean arterial blood pressure was restored from 11.0 +/- 2.4 kPa to 18.8 +/- 2.5 kPa by DHE due to a near twofold increase in systemic vascular resistance while cardiac output was unchanged. Hepatic arterial blood flow was reduced by 50% by a marked increase in hepatic arterial resistance above the pre-epidural value, while portal venous blood flow remained unchanged. Hepatic oxygen consumption decreased following DHE in spite of an increase in total oxygen consumption, probably partly due to a reduction in hepatic arterial oxygen availability. The mechanism by which the arterial blood pressure is restored by DHE in dogs during high epidural block must be regarded as unfavourable, especially with respect to the liver.

Haemodynamics and oxygen consumption in the dog during high epidural block with special reference to the splanchnic region.

High epidural block (Th I-IV) with bupivacaine was carried out in 16 dogs. Mean arterial blood pressure decreased to 52% of control value owing to nearly equal decreases in systemic vascular resistance and cardiac output. Portal venous blood flow decreased from 25.8 +/- 8.6 to 16.7 +/- 7.2 ml/kg b.w. X min-1 following epidural block, while hepatic arterial blood flow remained unchanged at 9.1 +/- 3.1 ml/kg b.w. X min-1 owing to a reduction in hepatic arterial resistance of 51%. Hepatic oxygen uptake was maintained during the epidural block through increased oxygen extraction. However, total oxygen uptake decreased by 18% and, in spite of this, arteriovenous oxygen content difference increased by 25%, indicating circulatory depression.

Haemotherapy with red-cell concentrates and a new red-cell storage medium.

The effects on plasma proteins and haemostasis of haemotherapy with buffy-coat-poor red-cell concentrate and red cells suspended and stored in a new medium containing sodium chloride, adenine, glucose, and mannitol (SAGM) were studied in elective surgery. In patients with normal preoperative serum albumin levels no transfusion of plasma was necessary before 50% of blood volume had been lost. When three different types of haemotherapy were investigated in patients undergoing orthopaedic surgery, it was found that when whole blood was replaced by red-cell concentrate and, later, by red-cell suspension in SAGM medium, the peroperative bleeding pattern did not change. The volume of transfused plasma was reduced by 47% in the red-cell-concentrate series and by 72% in the red-cell-suspension series. No albumin preparations were given and the use of red cells was decreased by 26%. Haemotherapy with red cells suspended in SAGM was useful in elective surgery and saved plasma for other purposes.