M.-E. Koller

Midazolam-fentanyl-isoflurane anaesthesia is suitable for haemodynamic and fluid balance studies in pigs

The domestic pig is a useful model in certain areas of biomedical research. Effective use of this species is often encumbered by lack of reference values in conscious as well as anaesthetized animals. Anaesthesia itself influences physiological and biological variables; the anaesthetic technique often affects experimental results. The relationship between anaesthesia and haemodynamics is well characterized in man, but less established in pigs. We studied the effect of midazolam-fentanyl-isoflurane anaesthesia in six immature, male, domestic pigs (Norwegian landrace). Haemodynamic variables (heart rate, arterial systolic, mean, diastolic pressures, pulmonary systolic, mean, diastolic pressures, pulmonary capillary wedge pressure), tissue perfusion, lymph flow (thoracic duct) were recorded for 3 h in animals with open chest through midline sternotomy. Variables relevant to fluid balance, e.g. interstitial hydrostatic pressure (Pi), serum-colloid osmotic pressure (s-COP) and serum-albumin (s-albumin) and -protein (s-protein) concentrations were measured. With the chosen anaesthetic technique haemodynamic variables, including lymph flow, and laboratory variables remained constant during the study period. Most variables were similar to conditions in humans. In contrast to adult humans exposed to the same anaesthetic technique, these pigs had lower haemoglobin-, s-albumin- and s-protein concentrations. A finding which may reflect immaturity. Liver and lung perfusion decreased significantly during the study period whereas perfusion of the other organs studied remained constant. Lack of responses to defined noxious stimuli during the study period suggest adequate analgesia. We conclude that midazolam, fentanyl and isoflurane provide cardiovascular stability including normal microvascular fluid exchange, which are essential elements for securing the quality of results obtained during cardiovascular research in anaesthetized pigs.

Neurogenic inflammation in rat trachea is accompanied by increased negativity of interstitial fluid pressure.

The present experiments were performed to investigate whether neurogenic inflammation in rat trachea (with edema formation and protein extravasation when the circulation is intact) induced by electrical field stimulation of neuropeptide-containing C fibers in the vagal nerve is accompanied by increased negativity of interstitial fluid pressure (P(if)). Increased negativity of P(if) in the trachea occurs in dextran anaphylaxis and mast cell degranulation and facilitates edema formation under these circumstances. Experiments were performed after circulatory arrest had been induced in pentobarbital anesthesia to prevent edema formation, which will raise P(if) and potentially cause underestimation of an increased negativity of P(if). After induction of circulatory arrest, the vagal nerve was isolated and placed in a stimulating electrode. The trachea was then exposed and covered with mineral oil, and measurement of P(if) was started as soon as possible thereafter. P(if) was measured with sharpened glass capillaries (tip diameter, 3 to 7 microns) connected to a servocontrolled counterpressure system. P(if) in the control group (n = 12) did not change throughout the observation period. Electrical stimulation of the left vagal nerve caused P(if) to fall in all experiments, from -1.1 +/- 1.1 mm Hg in the control condition to an average of -10.6 +/- 3.4 mm Hg (n = 9, P < .01). In some experiments, a continuous recording of P(if) was obtained, showing that the reduction of P(if) started within 30 seconds after onset of stimulation to reach and later remain at a stable level within a few minutes. The experimental protocol was repeated after the C fibers had been nearly depleted of neuropeptides with capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic evaluation of fluid shifts during normothermic and hypothermic cardiopulmonary bypass in piglets

Background: Edema, generalized overhydration and organ dysfunction commonly occur in patients undergoing open‐heart surgery using cardiopulmonary bypass (CPB) and induced hypothermia. Activation of inflammatory reactions induced by contact between blood and foreign surfaces are commonly held responsible for the disturbances of fluid balance (“capillary leak syndrome”). We used an online technique to determine fluid shifts between the intravascular and the interstitial space during normothermic and hypothermic CPB.

Studies on fluid extravasation related to induced hypothermia during cardiopulmonary bypass in piglets.

Background: Hypothermia, commonly used for organ protection during cardiopulmonary bypass (CPB), has been associated with changes in plasma volume, hemoconcentration and microvascular fluid shifts. Fluid pathophysiology secondary to hypothermia and the mechanisms behind these changes are still largely unknown. In a recent study we found increased fluid needs during hypothermic compared to normothermic CPB. The aim of the present study was to characterize the distribution of the fluid given to maintain normovolemia. In addition, we wanted to investigate the quantity and quality of the fluid extravasated during hypothermic compared to normothermic CPB.

Cardiac arrest due to massive pulmonary embolism following caesarean section. Successful resuscitation and pulmonary embolectomy

A woman developed pulmonary embolism with cardiac arrest after caesarean section. Cardiopulmonary resuscitation was performed for 45 min during which echocardiography showed right ventricular dilatation. After stabilization, but still in a critical condition, the patient was transferred by airambulance to a hospital with facilities for extracorporeal circulation. A massive embolus was removed. Some hours after extubation the patient developed respiratory insuffiency and hypovolaemia. Re‐intubation was followed by severe hypotension requiring external cardiac compression for about 15 min. An emergency explorative laparotomy revealed a ruptured liver with a subcapsular haematoma. A critical illness polyneuropathy made prolonged ventilatory support necessary. She recovered without cerebral sequelae.

Estimation of total body fluid shifts between plasma and interstitium in man during extracorporeal circulation

Fluid transport between plasma and interstitium during extracorporeal circulation was studied in seven patients undergoing aortocoronary bypass grafting. The absolute shifts in plasma volume during hypothermia were determined as the difference between input and loss of fluid and the changes in blood volume. The change in haemoglobin concentration due to acute haemodilution when starting extracorporeal circulation was used to calculate the absolute blood and plasma volume. The Starling equation for exchange across the capillary wall was used to describe fluid shifts. The total fluid filtered during the 60‐ to 90‐min period of extracorporeal circulation averaged 34.1 ± 11.1 (s.d.) ml/min. The total body filtration coefficient from the Starling relationship averaged 0.046 ± 0.012 ml/kg ± mmHg ± min (0.354 ± 0.092 ml/kg ± kPa ± min). Haemodilution, reducing colloid osmotic pressure in plasma (COPP) by approximately 10 mmHg (1.3 kPa) will result in a loss of plasma fluid of around 2 1 per hour. When corrected for lower fluid viscosity due to hypothermia during extracorporeal circulation, CFC would be about 40% higher, and a filtered volume of nearly 31 in a normothermic 70‐kg person would be expected. Crystalloid haemodilution for shorter periods of time does not produce excessive oedema and thus may be well tolerated.

Percutaneous placement of permanent central venous catheters: experience with 200 catheters

The prospective registration of 200 percutaneous placements of permanent central venous catheters (Hickman catheters and subcutaneous infusion ports) was conducted in 172 patients aged 3 months‐95 years. The insertions were reviewed to assess whether certain groups of patients or physicians were associated with more complications than others. Complications occurred in 16 patients (8. 0%), of which 12 were arterial punctures. Two attempts (1%) at catheter placement failed. None of the complications required treatment. Of the catheter placements, 70% were performed by one of the three authors, and the rest by seven other experienced anesthesiologists. The complication rates were not different between the two groups. Nor was the complication rate significantly higher in small children. Percutaneous placement of permanent central venous catheters thus proved to be a safe and reliable technique, even in small children. The method is easily learnt by physicians experienced in central venous catheterization. Using this method, permanent venous access may be offered to a large number of patients.

High-dose vecuronium may be an alternative to suxamethonium for rapid-sequence intubation

Endotracheal intubation conditions 60 s after intravenous administration of either high‐dose vecuronium (0.3 mg kg‐1; n = 25) or suxamethonium (1.0 mg kg‐1; n = 25) were compared in a blind, randomised study. No significant differences were found between the two drugs. In 96% of the patients intubation conditions were characterized as excellent or good. In only one patient (4%) in each group were intubation conditions unsatisfactory. According to our findings, high‐dose vecuronium provides satisfactory intubation conditions after 60 s and may be used instead of suxamethonium for rapid sequence intubation when a long duration of neuromuscular blockade is acceptable.

Midazolam does not potentiate the effect of vecuronium in patients

Reports of midazolam interaction with vecuronium in animals prompted us to compare midazolam (0.25 mg kg‐1) with thiopentone (5 mg kg‐1) for possible interactions with vecuronium in patients, when used for induction of anaesthesia. After the administration of either of the two induction agents, the patients received vecuronium 0.1 mg kg‐1. The onset time, duration of action and 25–75% recovery index of the neuromuscular blockade were recorded by measuring the force of thumb adduction evoked by ulnar nerve stimulation. We found no differences between patients receiving either midazolam or thiopentone in their response to vecuronium. In three of the ten patients receiving midazolam, the injection of this drug produced a 8–29% reduction of the initial twitch height.