Comparison of sevoflurane/fentanyl and isoflurane/fentanyl during elective coronary artery bypass surgery. Sevoflurane Venture Group.

PURPOSE: Due to the progressive aging of the surgical population, the proportion of patients with coronary artery disease (CAD) is likely to increase. The effects of the new inhalational anaesthetic sevoflurane must be determined in patients with known CAD. METHODS: This multicentre, randomized, open-label study compared the haemodynamic and cardiovascular effects of sevoflurane and isoflurane with fentanyl in 284 ASA physical status II-IV patients undergoing elective coronary artery bypass graft (CABG). RESULTS: Satisfactory records were available in 272 patients, 139 sevoflurane (Group S) and 133 isoflurane (Group I). There were no differences between groups for demographic data except that more patients in Group S were taking preoperative beta-blockers (P = 0.03). The mean end-tidal MAC and MAC.hr requirements between groups were not different (Group S received 0.63 +/- 0.02 MAC and 1.00 +/- 0.05 MAC. hr while Group I received 0.58 +/- 0.02 MAC and 0.92 +/- 0.05 MAC. hr P = NS). The preCPB use of intravenous fentanyl was not different between groups. There was a similar decrease in haemodynamic variables in both groups after induction that persisted throughout the preCPB period. The incidence of preCPB myocardial ischaemia, adverse haemodynamic events and use of vasoactive drugs did not differ between groups. The incidence of postoperative myocardial infarction was 2.2% for Group S and Group I was 4.5% (P = NS). There were five postoperative deaths, one of which was attributed to a cardiac cause (Group I). CONCLUSION: In patients undergoing elective CABG with low risk factors, either sevoflurane or isoflurane, combined with fentanyl, provided an acceptable preCPB haemodynamic profile and cardiac outcomes.

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.

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium.

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg.kg-1 (Group EDR-1), 0.25 mg.kg-1 (Group EDR-2), or 0.50 mg.kg-1 (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.

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.

Bolus administration of esmolol for controlling the haemodynamic response to tracheal intubation: the Canadian Multicentre Trial.

A multicentre trial was designed to determine the dose-response and side-effects of esmolol when administered as a single iv bolus prior to induction of anaesthesia for controlling the haemodynamic response to tracheal intubation. Five hundred and forty-eight patients from 12 university-affiliated centres across Canada were randomized prospectively to receive either placebo (PLAC) or esmolol (E) in a dose of 100 mg (E100) or 200 mg (E200). Study medication was given immediately before induction of anaesthesia with thiopentone 3-5 mg.kg-1 and succinylcholine 1.5 mg.kg-1. Low-dose narcotic (fentanyl 2-3 micrograms.kg-1 or sufentanil 0.3 micrograms.kg-1) or moderate dose narcotic (fentanyl 4-7 micrograms.kg-1) was also given at five of the participating centres, whereas patients in the remaining seven centres received no narcotic. Patients who received PLAC and no narcotic had greater HR and SBP values after tracheal intubation than patients who received either E100 or E200 (P less than 0.005). The proportion of patients whose maximum HR exceeded 110 min-1 was also greater in the PLAC group (22/180) than in either the E100 (10/187) or E200 (9/181) groups (P less than 0.05), but was not different when comparing E100 with E200. Esmolol was less effective in controlling blood pressure, but, in combination with low-dose narcotic, esmolol suppressed the SBP response to tracheal intubation. In the presence of moderate-dose narcotic, however, a decrease in SBP occurred in all three groups following induction of anaesthesia (P less than 0.003), with the largest decrease (17 +/- 4%) occurring in patients who had received E200. The overall incidence of hypotension (SBP less than 90 mmHg) was greater in the E200 group (33%) than either the E100 (25%) or PLAC (16%) groups (P less than 0.05). Other side-effects, such as bradycardia, bronchospasm or pain on injection, occurred no more frequently in either esmolol group than with placebo. It is concluded that a 100 mg bolus of esmolol is safe and effective for controlling the haemodynamic response to tracheal intubation. This dose of esmolol combined with a low dose of narcotic (fentanyl 2-3 micrograms.kg-1 or equivalent) results in effective control of both heart rate and blood pressure, while avoiding important side-effects.

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)

A randomized double-blind comparison of fentanyl- and sufentanil-oxygen anesthesia for abdominal aortic surgery.

Twenty-four patients undergoing abdominal aortic surgery for aneurysm or occlusive vascular disease entered a randomized, double-blind protocol comparing high-dose narcotic anesthesia with fentanyl (125 micrograms/kg) or sufentanil (25 micrograms/kg). All patients received perioperative beta-adrenergic blockade therapy. Hemodynamic and electrocardiographic (leads II and V5) responses to induction, intubation, skin incision, aortic cross-clamping, and declamping were studied. Sufentanil produced a transient decrease in mean arterial pressure and a significant reduction of systemic vascular resistance during induction. However, no significant hemodynamic differences were observed between the two groups during intubation, or at any other time during surgery. To maintain mean arterial pressure within 20% of the awake control value, the fentanyl group required an average infusion of 1.0 +/- 1.1 micrograms/kg/min of nitroglycerin compared with 1.7 +/- 2.8 micrograms/kg/min for the sufentanil group. Low-dose isoflurane was required in 30% of patients in the fentanyl group, compared with 41% of the sufentanil group, for control of blood pressure. The multiple-bolus technique of narcotic administration resulted in a wide but parallel range of plasma concentrations from induction to the end of surgery with both narcotics. Mean plasma fentanyl concentrations varied between 7.2 +/- 1.4 ng/mL and 26.5 +/- 7.9 ng/mL, and mean sufentanil plasma concentrations varied between 1.0 +/- 0.1 ng/mL and 10.6 +/- 7.2 ng/mL throughout surgery. Within this range of narcotic serum levels, the authors were unable to identify a specific threshold level for either narcotic above which hemodynamic responses were consistently attenuated. A low incidence (4.5%) of intraoperative myocardial ischemia was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Bolus administration of esmolol for the treatment of intraoperative myocardial ischaemia.

We report the successful treatment with esmolol of intraoperative myocardial ischaemia associated with concurrent hypertension and tachycardia, in a patient with risk factors for coronary artery disease undergoing peripheral vascular surgery. The pathophysiology of myocardial ischaemia, and the therapeutic role of beta blocking drugs are briefly reviewed. Esmolol, a short-acting cardioselective beta blocking drug, was administered in a bolus of 1.5 mg.kg-1, and resulted in prompt resolution of the haemodynamic abnormalities, with concomitant restitution of the ST segments to isoelectric baseline. We conclude that bolus administration of esmolol is practical and can be effective for the treatment of intraoperative myocardial ischaemia.