Treatment of intrathecal morphine-induced pruritus following caesarean section.

PURPOSE: To compare both the efficacy and cost of nalbuphine and diphenhydramine in the treatment of intrathecal morphine-induced pruritus following Caesarean section. METHODS: Eighty patients, undergoing elective Caesarean section under spinal anaesthesia, were randomized, in a prospective, double-blind trial, to receive either nalbuphine (Group NAL) or diphenhydramine (Group DIP) for the treatment of SAB morphine-induced pruritus. All patients received an intrathecal injection of 10-12 mg hyperbaric bupivacaine 0.75% and 200 micrograms preservative free morphine. Postoperative pruritus was assessed, using a visual analogue scale (VAS), for 24 hr. Pruritus treatment was administered upon patient request and by a nurse blinded to the treatment given. Patients who failed to respond to three doses of the study drug were deemed treatment failures. Patient satisfaction was assessed with a questionnaire given 24 to 48 hr after surgery. Direct drug costs were calculated based on the pharmacy provision costs as of April 1996. RESULTS: Eighty patients were enrolled and 45 requested treatment for pruritus. Patients treated with NAL (n = 24) were more likely to achieve a VAS score of zero with treatment (83% vs 43%, P < 0.01), had a higher delta VAS following treatment (4 +/- 2 vs 2 +/- 2, P < 0.003), and experienced fewer treatment failures (4% vs 29%, P < 0.04), than those treated with DIP (n = 21). Group NAL patients were also more likely to rate their pruritus treatment as being good to excellent (96% vs 57%, P < 0.004). Direct drug costs were higher for NAL than for DIP ($6.4 +/- 3.1 vs $1.7 +/- 0.7, respectively, P < 0.0001). CONCLUSION: Nalbuphine is more effective than diphenhydramine in relieving pruritus caused by intrathecal morphine and the cost differences are small.

Cost-effectiveness of inhalational, balanced and total intravenous anaesthesia for ambulatory knee surgery.

PURPOSE: A randomized, blinded clinical trial was undertaken to compare recovery characteristics and cost-benefits associated with three general anaesthetic techniques for arthroscopic knee surgery in an ambulatory care setting. METHODS: Ninety three, ASA Physical Status I-II patients were randomly allocated to receive one of three types of general anaesthesia: isoflurane/fentanyl/N2O (Group INH); alfentanil/N2O (Group BAL); or propofol/alfentanil/O2 (Group TIVA). Postoperative recovery profiles were evaluated at 30, 60, 90 and 120 min after emergence from anaesthesia, and direct and indirect costs of each anaesthetic were compared. RESULTS: The most rapid emergence was observed in Group BAL (2.2 +/- 1.5 min, P < 0.0001 compared with groups INH and TIVA), although the incidence of post-operative nausea and vomiting was also highest in this group (P = 0.02 compared with groups INH and TIVA). However, overall patient satisfaction, and mean times to discharge from the Post Anesthesia Recovery Unit and hospital, were rapid and similar in all three groups. During anaesthesia which lasted 40-45 min, nearly a four-fold difference was observed in the direct costs of anaesthetic drugs: $16.4 +/- 4.4 (Group INH), $45.3 +/- 11.4 (Group BAL) and $63.4 +/- 17.9 (Group TIVA, P < 0.001 between groups); while indirect costs were similar. CONCLUSIONS: For arthroscopic knee surgery, INH anaesthesia with isoflurane/fentanyl/N2O is associated with similar hospital discharge times, and comparable levels of patient satisfaction as either BAL or TIVA. While indirect costs were similar, lower direct costs suggest that there may be a pharmacoeconomic benefit associated with the use of a "standard" isoflurane/fentanyl/N2O anaesthetic in certain day care surgery procedures.

Midazolam and awareness with recall during total intravenous anaesthesia.

PURPOSE: A double-blind study was undertaken to evaluate the influence of graded doses of midazolam on propofol infusion requirements, recovery characteristics and the quality of recovery, associated with propofol/alfentanil/O2 total intravenous anaesthesia (TIVA). METHODS: Ninety ASA Class I and II subjects scheduled for arthroscopic knee surgery were randomly allocated to receive either placebo (Group PLAC), or midazolam doses of 15, 30 or 45 micrograms.kg-1 (Groups M-15, M-30 and M-45, respectively). Anaesthesia was induced and maintained with propofol (infused initially at 100 micrograms.kg-1.min-1, and adjusted there after according to anaesthetic depth) and alfentanil (loading dose of 20 micrograms.kg-1, followed by infusion at 0.5 microgram.kg-1. min-1). Postoperatively, times to awakening, recovery, and discharge were evaluated, in addition to psychometric evaluations using the Trieger Dot Test (TDT). RESULTS: The study was discontinued prematurely, as six patients unexpectedly experienced intraoperative awareness with recall (4/21 = 19.1% of patients with PLAC vs 2/69 = 2.9% of patients in the midazolam groups, P < 0.04). Induction requirements of propofol were found to be lower in the M-30 and M-45 groups when compared with PLAC (P < 0.05), whereas propofol infusion requirements were similar among groups. Times to awakening and discharge from the Recovery Room and Day Care Unit, as well as TDT scores, were no greater in any midazolam group than in PLAC. CONCLUSIONS: Midazolam 30-45 micrograms.kg-1 decreases the amount of propofol required for anaesthetic induction, without influencing recovery profiles or patient discharge times from the Day Care Unit. Despite careful modulation of the propofol infusion rate, six patients unexpectedly experienced intraoperative awareness with recall, with the lowest incidence occurring in those groups where patients had received midazolam.

Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion.

A randomized, double-blind study was undertaken to determine the dose requirements, recovery characteristics, and pharmacokinetic variables of midazolam given by continuous infusion for sedation in patients following abdominal aortic surgery. Thirty subjects, 50-75 yr, scheduled to undergo aortic reconstructive surgery, entered the study. Following a nitrous oxide-isoflurane-opioid anaesthetic technique, patients were randomly allocated to receive one of three loading doses (0.03, 0.06 or 0.1 mg.kg-1) and initial infusion rates (0.5, 1.0 or 1.5 micrograms.kg-1.min-1) of midazolam, corresponding to groups low (L), moderate (M) and high (H). The infusion of midazolam was adjusted to maintain sedation levels of "3, 4 or 5," which permitted eye opening in response to either verbal command or a light shoulder tap, using a seven-point scale ranging from "0" (awake, agitated) to "6" (asleep, non-responsive). Additionally morphine was given in increments of 2.0 mg iv prn for analgesia. On the morning after surgery, midazolam was discontinued, and the tracheas were extubated when patients were awake. Blood samples were taken during, and at increasing intervals for 48 hr following discontinuation of the infusion, and analyzed by gas chromatography. The desired level of sedation was maintained during more than 94% of the infusion period in all three groups, with a maximum of three dose adjustments per patient, for treatment which lasted 16.3 +/- 0.6 hr. There was, however, an increase in both the infusion rates and mean plasma concentrations from Group L to Group H (P < 0.05), which corresponded to an inverse relationship of morphine requirements during the period of sedation (P < 0.05, Group H vs Group L). Optimal midazolam infusion rates and resulting plasma concentrations at the times the infusions were discontinued (in parentheses) were as follows-Group L: 0.60 +/- 0.18 microgram.kg-1.min-1 (76 +/- 32 ng.mL-1), Group M: 0.90 +/- 0.52 microgram.kg-1.min-1 (133 +/- 71 ng.mL-1), and Group H: 1.34 +/- 0.69 microgram.kg-1.min-1 (206 +/- 106 ng.mL-1). Times to awakening were longer in Group H: 3.1 +/- 3.4 hr, than in Group L: 1.1 +/- 0.8 h, P < 0.05. Pharmacokinetic variables were found to be dose-independent over the range of infusion rates. Mean values were t1/2 beta = 4.4 +/- 1.5 hr, CL = 5.94 +/- 1.69 mL.min-1.kg-1, Vd = 3.13 +/- 1.07 L.kg-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of alfentanil on the hemodynamic and catecholamine response to tracheal intubation.

A randomized, placebo-controlled study was conducted in 60 ASA Class I, II, and III patients to determine the dose response of alfentanil in moderating the cardiovascular and catecholamine response to tracheal intubation (INT). Patients were randomly allocated into one of four groups to receive either 15 micrograms/kg alfentanil (A15), 30 micrograms/kg alfentanil (A30), 45 micrograms/kg alfentanil (A45), or normal saline (control), given intravenously (i.v.) before induction of anesthesia. One minute after administration of 4.0 mg/kg thiopental and 1.5 mg/kg succinylcholine i.v., tracheal intubation was performed using direct laryngoscopy. In response to INT, increases in heart rate, systolic blood pressure, and systemic vascular resistance occurred in the control group. These changes were significantly more than corresponding changes of heart rate, systolic blood pressure, and systemic vascular resistance in all three alfentanil groups (P < 0.05). In contrast, cardiac index and ejection fraction decreased moderately in every group during the study period, but there were no differences among groups with respect to either cardiac index or ejection fraction at corresponding times following INT. In the control group, epinephrine and norepinephrine serum concentrations increased by 152 +/- 52% and 58 +/- 62%, respectively, following INT (different from A30 and A45, P < 0.05). However, up to a dose of 30 micrograms/kg (A30), a dose-dependent decrease in the maximum percent changes of both epinephrine and norepinephrine occurred in response to INT. A larger dose of alfentanil was no more efficacious as the catecholamine response to tracheal intubation was not significantly different when comparing the A45 and A30 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cumulation and reversal with prolonged infusions of atracurium and vecuronium.

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of transcutaneous end-tidal and arterial measurements of carbon dioxide during general anaesthesia.

A randomized, prospective study was performed to evaluate the accuracy of a new transcutaneous carbon dioxide (CO2) monitor (Fastrac) during general anaesthesia. Twenty-two adult patients undergoing elective surgery were subjected to three different levels of minute ventilation by varying their respiratory rates in a randomized cross-over design. Simultaneous measurements of transcutaneous CO2 (PTCCO2) and arterial CO2 (PaCO2) were obtained at three levels of minute ventilation (low, medium and high). End-tidal CO2 (PETCO2) values were also recorded from a mass spectrometer (SARA) at each time period. A total of 66 data sets with PaCO2 ranging from 28-62 mmHg were analyzed. The PTCCO2 values demonstrated a high degree of correlation with PaCO2 over the range of minute ventilation (y = 0.904x + 6.36, r = 0.92, P less than 0.001). The PETCO2 measurement also demonstrated a generally good correlation with PaCO2 (y = 0.62x + 9.21, r = 0.89, and P less than 0.01). However, the PETCO2-PaCO2 gradients (mean 7.0 +/- 3.1 mmHg) were greater than the PTCCO2-PaCO2 gradients (mean 2.3 +/- 2.4 mmHg) at all three levels of minute ventilation (P less than 0.05). These differences were greatest when PaCO2 was in the high range (48-60 mmHg). We conclude that the new Fastrac CO2 monitor is accurate for monitoring carbon dioxide levels during general anaesthesia. The new transcutaneous devices provide an effective method for non-invasive monitoring of CO2 in situations where continuous, precise control of CO2 levels is desired.

Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery.

A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs.

Alfentanil controls the haemodynamic response during rapid-sequence induction of anaesthesia.

Laryngoscopy and tracheal intubation often cause hypertension and tachycardia, which may be exaggerated during rapid-sequence induction of anaesthesia. A placebo-controlled, double-blind study was conducted in 60 patients to determine dose-response and effects on myocardial performance of alfentanil when used to attenuate this cardiovascular response. Patients were divided into four groups to receive a pre-induction bolus from a coded syringe, which contained either normal saline (PLAC), alfentanil 30 micrograms.kg-1 (ALF 30), alfentanil 45 micrograms.kg-1 (ALF 45) or alfentanil 60 micrograms.kg-1 (ALF 60). Anaesthesia was induced in rapid sequence with thiopentone 4.0 mg.kg-1 and succinylcholine 1.5 mg.kg-1, and the trachea was intubated 60 sec later. Increases in heart rate (21 +/- 10 bpm), mean arterial pressure (28 +/- 13 mmHg), and systemic vascular resistance index (1420 +/- 780 dynes.sec-1.cm-5) were observed in response to intubation with PLAC but in none of the 3 ALF groups (P less than 0.05). However, heart rate and mean arterial pressure decreased significantly in both the ALF 45 and ALF 60 groups (P less than 0.05), whereas ALF 30 resulted in no change in these variables over time. Cardiac index, stroke volume index, and ejection fraction tended to decrease in all four groups, but none of these variables was different at corresponding time when comparing the ALF groups with PLAC.(ABSTRACT TRUNCATED AT 250 WORDS)