Search

OBJECTIVE: To examine the effects of cardiopulmonary bypass (CPB) on total and unbound plasma concentrations of propofol and midazolam when administered by continuous infusion during cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four adult patients undergoing cardiac surgery. INTERVENTIONS: Patients received either propofol or midazolam to supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1 mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam, 0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood sample were collected from the radial artery cannula at 0, 2, 4, 8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6, 10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and unbound propofol and midazolam concentrations were determined by ultrafiltration and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total propofol and midazolam plasma concentrations, but the unbound concentrations remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to 0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to 11.2 +/- 2.1%. CONCLUSIONS: Unbound concentrations of propofol and midazolam are not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms do not need to be changed to achieve stable unbound plasma concentrations when initiating CPB.

The effect of adding a continuous infusion of morphine 1 mg/hr to patient-controlled intravenous analgesia was studied in a randomized double-blind trial. Ninety-six patients scheduled for abdominal surgery were enrolled; 38 received PCA and continuous infusion (PCA + C), 45 received PCA alone and 13 were excluded because of protocol violations. PCA was delivered via an ABBOTT 4200 pump with settings of morphine 1 mg bolus and five-minute lockout in both groups. A separate pump delivered a continuous infusion of morphine 1 mg/ml (PCA + C) or 9% normal saline (PCA) at 1 ml/hr for three postoperative days. Pain was assessed by hourly verbal pain scores (VPS) and daily visual analog pain scores at rest and on movement (VASrest, VASmove). PCA delivered morphine and the demand to delivery ratio (D/D ratio) were used as indirect indicators of pain. These were assessed during daytime (0800–2200 hours), sleep (2200–0500 hours) and on first waking (0500–0800 hours). Patient demographics were similar. Patients receiving a continuous infusion had lower pain scores during the first 24 hours but not thereafter (VPS P=0.04, VASmove P=0.02). The PCA group delivered more PCA morphine during 0500–0800 hours and 0800–2200 hours on the first day only. There was no significant difference in the D/D ratio for any time period during the three days. Total morphine delivery was greater in the PCA + C group on the second and third postoperative days (P= 0.009 and P=0.0001 respectively). The incidence of respiratory depression and the total number of complications were significantly higher in those receiving continuous infusion (P=0.04 and P=0.011 respectively.) Adding a continuous morphine infusion of 1 mg/hr to the described PCA settings for three days following abdominal surgery improved analgesia during the first 24 hours but was associated with a greater incidence of complications.

Epidural analgesia offers patients a state close to ‘no pain' following surgery. The pharmacology of epidural opioids, local anaesthetics, combination therapy and newer agents is discussed. Combination local anaesthetic-opioid solutions provide superior analgesia to other techniques. Patients for epidural management can be selected based on surgical procedure and concurrent illness. A conservative approach is recommended and practical issues of implementing epidural management in postoperative surgical wards is discussed.

L-arginine cardioplegia decreases biochemical markers of myocardial damage and oxidative stress in patients with normal left ventricular function. We investigated the effects of L-arginine supplemented cardioplegic arrest in patients with reduced ejection fraction. Fifty-three adult patients with left ventricular ejection fraction −1 (15 minutes) (P=0.0004). Superoxide dismutase activity was higher in L-arginine group, 229±87 vs 191.3±68 (5 minutes), 229±54 vs 198±15 nmol.minute−1.ml (15 minutes) (P=0.005). Lactic acid flux was lower in the L-arginine group, 0.15±0.23 vs 0.48±0.32 (1 minute), 0.08±0.19 vs 0.38±0.31 (5 minutes) and −0.15±0.13 vs 0.26±0.30 mmol.l−1 (15 minutes), (P=0.0003). There was no difference in left ventricular systolic function. The mitral annular tissue Doppler inflow (eʹ) velocity during early diastole improved in the L-arginine group following cardiopulmonary bypass (control 4.2±1.9 cm.s−1 to 3.6±1.2 cm.s−1 vs L-arginine 3.8±1.2 cm.s−1 to 4.6±1.4 cm.s−1) (P=0.018). In patients with reduced ejection fraction, L-arginine supplemented cardioplegic arrest did not affect postoperative cardiac troponin-I levels, but attenuated cardiac cellular peroxidation and improved early left ventricular diastolic function.

Interpleural infusions (24 hr) were given to 14 adults (29-81 yr) having surgery via right subcostal incisions. Patient-controlled analgesia with morphine was also available for 72 hours following surgery. An infusion of 0.25% bupivacaine with adrenaline 1/400,000 was commenced at 0.1 ml/kg/hr at the conclusion of surgery after an initial 20 ml bolus. The 24 hr cumulative morphine dose increased by 62% (P < 0.01) on the second postoperative day after the bupivacaine infusion was ceased, but the pain score did not change. There was no clinical evidence of bupivacaine toxicity although the maximum bupivacaine concentration ranged from 0.74-6.52 mg/l, mean 2.90 (SEM 0.44) mg/l and vascular uptake was rapid in two patients. The concentration of S-bupivacaine was consistently greater than R-bupivacaine (P < 0.05) and total body clearance was less. The unbound bupivacaine fraction also changed from 3.6% (SEM 0.6) at the start of the infusion to 2.0% (SEM 0.3) at 24 hr (P < 0.005). The total body clearance of each enantiomer was reduced during the 24 hours (P < 0.001). No relationship between pharmacokinetic parameters and weight, age or sex was found (P>0.25 for each). Variation between patients was reduced when parameters were estimated for the free (unbound) bupivacaine (P < 0.001).

The dosage, haemodynamic and respiratory effects of propofol for laryngeal mask airway (LMA) insertion were investigated. Fifty patients (ASA I-II) were randomly assigned one of four induction doses of propofol (1.5–2.5 mg/kg) delivered over 30 seconds and the first attempt at LMA insertion was made at 90 seconds. The LMA was inserted at 90 seconds in 35 patients and by 300 seconds in 13 others (mean plasma concentration at 90 seconds was 7.7 mcg/ml (no delay) versus 5.2 mcg/ml (insertion delayed), P < 0.01). Insertion was less successful after 1.5 mcg/kg (failed at 90 seconds in 6 of 12 patients), but did not vary with the other doses. Additional propofol (0.5 mg/kg/30s) was required in 22 patients for LMA insertion or to prevent movement, resulting in propofol concentrations at 120–180 seconds above 7 mcg/ml. Respiratory effects were minor, but MAP decreased by 18±1.4 mmHg at 90 seconds. Cardiovascular effects did not differ significantly between dosage groups or with the use of additional propofol.

We have assessed, in 200 patients, the determinants of the reversal time of competitive neuromuscular block by anticholinesterase when alcuronium and atracurium neuromuscular block were antagonized by neostigmine 0.04 and 0.08 mg kg-1 and edrophonium 0.5 and 1.0 mg kg-1. A biexponential relationship was found between the reversal time (time from injection of anticholinesterase to a train-of-four ratio of 70%) and the degree of neuromuscular block at reversal (all groups; F ratio, P less than 0.05). Reversal time was determined by two processes: direct antagonism by the anticholinesterase and spontaneous recovery of the neuromuscular blocking agent, with the latter becoming the major determinant at profound levels of neuromuscular block (0-10% of control twitch height). Neostigmine, in the doses studied, appeared to have a higher "ceiling" of neuromuscular block which it completely antagonized, although edrophonium had a more rapid onset of action. The reversal time for alcuronium became progressively longer relative to atracurium as neuromuscular block increased because of the slower spontaneous recovery rate. Avoidance of profound neuromuscular block at the completion of surgery is required to ensure reliable antagonism of the block within 5-10 min by an anticholinesterase. Neostigmine 0.08 mg kg-1 was found to be the most effective agent in antagonizing profound neuromuscular block.

We have assessed the effect of i.m. ketorolac or morphine on early postoperative gastric emptying of liquids in patients undergoing orthopaedic surgery with spinal anaesthesia. Liquid gastric emptying was measured by absorption of paracetamol with patients acting as their own controls. There was no delay after ketorolac 30 mg, but morphine 10mg resulted in marked delay. There was no difference in postoperative visual analogue pain scores between treatments. (Br. J. Anaesth. 1995; 74: 257–260).

Fentanyl and bupivacaine were tested for their stability when diluted with 0.9% sodium chloride to 4 micrograms ml-1 and 0.1% respectively, in 100-ml polyvinyl chloride (PVC) bags, alone and in combination, with and without adrenaline 1:200,000. Changes in drug concentration and pH were investigated for 56 days. The combination of fentanyl, bupivacaine and adrenaline was tested under varying environmental conditions of 35 degrees C, 4 degrees C, -18 degrees C, room temperature, darkness and after autoclaving. Fentanyl and bupivacaine were adsorbed onto PVC, resulting in reductions of 12.6% and 9.6% drug mass, respectively, at day 3, but remained stable thereafter. Adrenaline was progressively degraded to a maximum reduction of 37.3% at 35 degrees C by day 56. Solutions containing adrenaline became more acidic over 56 days. Fentanyl and bupivacaine were stable.

Twenty patients were given maximal doses of atracurium or vecuronium by infusion during surgery. Anaesthesia was maintained with an infusion of thiopentone, nitrous oxide and fentanyl. In patients administered atracurium, the plasma laudanosine concentration at cessation of surgery was 0.34 (SD 0.22) micrograms ml-1; there was little tendency to cumulate during operation. A 20% higher arterial concentration of thiopentone was found at awakening in patients given atracurium, suggesting CNS stimulation by laudanosine, although the effect is too modest to be of clinical significance.