Heart rate variability response to standing in men and women receiving d,l-sotalol following coronary artery bypass graft surgery.

Heart rate variability (HRV), a quantitative marker of autonomic control of heart rate (HR), declines in men and women following coronary artery bypass graft (CABG) surgery. Although d,l-sotalol is prescribed following CABG surgery primarily for its antiarrhythmic effect, its effects on HRV have not been reported; the ß-adrenergic antagonist effect of d,l-sotalol may attenuate sympathetically mediated HR and blood pressure (BP) responses to standing, resulting in postural hypotension. In this study, the HRV response to standing 4 days following CABG surgery in men and women prescribed d,l-sotalol was measured to examine the influence of d,l-sotalol on previously reported HRV responses, taking age and gender into consideration. Participants included 28 men and 10 women who completed testing in supine and standing postures; all had received low-dose d,l-sotalol daily since the first postoperative day. Data included continuous electrocardiograph recording of R-R interval for 10 min in each posture. Participants showed significant effects of standing on the autonomic modulation of HR, as seen by a decrease in parasympathetic indices and R-R interval and an increase in BP. In men, standing decreased parasympathetic modulation and increased the sympathetic nervous system indicator, but previously reported age effects were not seen. In women, standing decreased low frequency power and R-R interval and increased BP, with older women having a smaller increase in BP, suggesting an attenuated response. The differential autonomic nervous system modulation of HR as a function of gender and age after CABG surgery may be attenuated by d,l-sotalol.

The addition of fentanyl does not alter the extent of spread of intrathecal isobaric bupivacaine in clinical practice.

PURPOSE: Fentanyl is commonly added to intrathecal local anesthetic solutions. In vitro data has shown fentanyl to render isobaric local anesthetics hypobaric, and alter the spread in artificial cerebrospinal fluid. This study examined whether the addition of fentanyl to isobaric bupivacaine with morphine leads to a clinically important alteration in the extent of spread of anesthesia. METHODS: Forty-four ASA I-III patients undergoing lower limb orthopedic procedures completed this double-blind, placebo-controlled trial. Patients were randomized into one of two groups, receiving intrathecal bupivacaine 15 mg and preservative-free morphine 200 microg without (Control group), or with the addition of fentanyl 0.02 mg (Fentanyl group). Patients were maintained at a slight head-up tilt. Variables studied over three hours included sensory level to cold and pinprick, motor blockade (Bromage scale), and circulatory data. RESULTS: No differences existed between the Fentanyl and Control groups with respect to highest level of block for cold: T4 (T2-T5) vs T3.5 (T3-T8) respectively (median, 95% confidence interval) or pinprick: T4 (T3-T6) vs T4.5 (T3-T8). Similarly, there was no difference in the time taken to reach maximum block height to cold (20 +/- 9 vs 23 +/- 13 min, mean +/- SD) or pinprick (20 +/- 9 vs 24 +/- 13 min). CONCLUSION: The addition of fentanyl 0.02 mg to 0.5% bupivacaine with morphine does not affect the maximal block height or time to maximal block in clinical practice.

Autonomic circulatory and cerebrocortical responses during increasing depth of propofol sedation/hypnosis in humans.

PURPOSE: To describe the relative effects of graded central nervous system (CNS) depression, using increasing propofol infusion rates, on neurovegetative brainstem-mediated circulatory control mechanisms and higher cortical activity in healthy humans. METHODS: Propofol was administered using an infusion scheme designed to achieve three target blood concentrations in ten healthy volunteers. Blood propofol concentrations and sedation scores were determined at baseline, during the three propofol infusion levels, and 30 min into the recovery period. Electroencephalographic (EEG) power was measured in three frequency bands to quantify cortical activity, and autonomic heart rate control was quantified using spontaneous baroreflex assessment and power spectral analysis of pulse interval. RESULTS: Sedation scores closely paralleled propofol blood concentrations (0, 0.53 +/- 0.34, 1.24 +/- 0.21, 3.11 +/- 0.80, and 0.96 +/- 0.42 microg x mL(-1) at baseline, three infusion levels and recovery respectively), and all subjects were unconscious at the deepest level. Indices of autonomic heart rate control were decreased only at the deepest levels of CNS depression, while EEG effects were apparent at all propofol infusion rates. These EEG effects were frequency specific, with power in the beta band being affected at light levels of sedation, and alpha and delta power altered at deeper levels. CONCLUSIONS: The results of this study support a relative preservation of neurovegetative circulatory control mechanisms during the early stages of CNS depression using gradually increasing rates of infusion of propofol. Indices of circulatory control did not reliably reflect depth of sedation.

An unexpected benefit of pre-emptive rectal analgesic administration: the "key" to postoperative analgesia.

Analgesic and anti-inflammatory drugs are frequently administered intraoperatively by the rectal route to provide pre-emptive postoperative analgesia. We report the case of an inmate of a federal penitentiary who underwent orthopedic surgery in a public hospital. After induction of general anesthesia, indomethacin and acetaminophen were administered rectally. This led to the incidental discovery of a handcuff key hidden in the rectum and, thereby, the prevention of a planned escape. A review of data regarding escapes by prisoners from public hospitals is provided, as well as a description of cases of patients presenting with foreign rectal objects. A number of benefits have been described for the use of pre-emptive analgesia. This is the first reported description of an incidental benefit: the prevention of a planned escape by a prison inmate.

Post discharge nausea and vomiting after ambulatory laparoscopy is not reduced by promethazine prophylaxis.

PURPOSE: To determine the incidence of post-discharge nausea and vomiting (PDNV) following outpatient laparoscopic procedures in women, and to assess the efficacy of the prophylactic administration of promethazine prior to discharge from hospital. METHODS: Ninety-five healthy women scheduled for ambulatory laparoscopic cholecystectomy or gynecological surgery completed this double blind, placebo controlled study. A standardized fentanyl-propofol-nitrous oxide-isoflurane anesthetic was used, and all patients received 0.5 mg droperidol i.v., intraoperatively. Subjects were randomized to receive 0.6 mg x kg(-1) promethazine or placebo i.m. prior to transfer from the post-anesthetic recovery (PAR) unit. The incidence and severity of nausea, pain, and drowsiness were documented using patient diaries at four time intervals during the first 24 hr postoperatively using four-point self-assessment scales. RESULTS: After discharge home, the overall incidence of nausea was 48%, moderate to severe nausea 30%, vomiting 17% and rescue antiemetic use 28%, with no difference between those receiving saline or promethazine. The need for antiemetics in the PAR was associated with subsequent PDNV, with those requiring PAR antiemetics being four times as likely to vomit after discharge (P = 0.008). CONCLUSION: Despite the prophylactic administration of 0.5 mg droperidol i.v., patients undergoing ambulatory laparoscopic surgery reported a high incidence of nausea after discharge. Patients requiring antiemetics in the PAR were at higher risk for PDNV. The incidence of nausea was not altered by prophylactic administration of 0.6 mg x kg(-1) promethazine i.m. before discharge.

The effects of clonidine on sensitivity to phenylephrine and nitroprusside in patients with essential hypertension recovering from surgery.

UNLABELLED: Clonidine reduces postoperative circulatory instability in patients with essential hypertension. It also increases the sensitivity to vasopressors before and during anesthesia. We investigated blood pressure responses to phenylephrine and nitroprusside pre- vs postoperatively and the effect of clonidine on these responses in patients with essential hypertension. Twenty patients received clonidine 6 microg/kg orally 120 min before anesthesia and 3 microg/kg IV over the final hour of surgery or an identical placebo. During increasing bolus doses of phenylephrine and nitroprusside (30-300 microg), the maximal systolic pressure responses were recorded at baseline on the day before surgery, before the induction of anesthesia, and 1 and 3 h postoperatively. Sensitivity to phenylephrine and nitroprusside was interpolated from linear regression of the data. There was no difference between preoperative and postoperative sensitivity to phenylephrine or nitroprusside in either group. Clonidine increased sensitivity to phenylephrine versus placebo before and after surgery (response to dose of 1.5 microg/kg: 42+/-14 vs 27+/-8 mm Hg preinduction, 37+/-10 vs 26+/-8 mm Hg 3 h postoperatively; both P < 0.01), but not to nitroprusside (38+/-6 vs 37+/-10 mm Hg preinduction and 40+/-6 vs 39+/-8 mm Hg postoperatively). Clonidine increases the sensitivity to phenylephrine but not nitroprusside at baseline and postoperatively in hypertensive patients. IMPLICATIONS: Clonidine increases the sensitivity to bolus injections of the vasoconstrictor phenylephrine, but not the vasodilator sodium nitroprusside, before and after surgery in patients with preexisting hypertension. The doses of vasopressors should be reduced accordingly in hypertensive patients receiving perioperative clonidine.

Addition of opioids alters the density and spread of intrathecal local anesthetics? An in vitro study.

PURPOSE: To determine whether the addition of opioids alters the density and spread of intrathecal local anesthetics in vitro. METHODS: In Part I, the densities of hyperbaric bupivacaine 0.75% (HB), hyperbaric lidocaine 5% (HL) and isobaric bupivacaine 0.5% (IB) with and without morphine (M), and fentanyl (F) were measured at 22 degrees C. In Part II a model was constructed utilizing a column containing a solution similar in composition to cerebrospinal fluid (CSF) at 37 degrees C. The various local anesthetic-opioid solutions, coloured with crystalline methylene blue dye, were injected at 22 degrees C into the column at a controlled rate through a spinal needle. The direction and extent of spread of the injectates were compared. RESULTS: The relative densities of the five solutions were: HB = HL > IB > M > F. The addition of fentanyl to IB reduced the density of the final solution (P < 0.05). In the model, IB alone and IB with morphine showed mainly downward spread, with the addition of fentanyl to IB resulting in upward movement (P = 0.004). The hyperbaric local anesthetics moved downward with or without opioids. CONCLUSION: The addition of fentanyl reduces the density of IB in vitro and alters its movement in simulated CSF. This may prove to be important in predicting the level of spinal block in clinical practice.

Cardiac baroreflex during the postoperative period in patients with hypertension: effect of clonidine.

BACKGROUND: Patients with essential hypertension show altered baroreflex control of heart rate, and during the perioperative period they demonstrate increased circulatory instability. Clonidine has been shown to reduce perioperative circulatory instability. This study documents changes in measures of heart rate control after surgery in patients with essential hypertension and determines the effects of clonidine on postoperative heart rate control in these patients. METHODS: Using a randomized double-blind placebo-controlled design, 20 patients with essential hypertension (systolic pressure >160 mm Hg or diastolic pressure >95 mm Hg for > or =1 yr) were assigned to receive clonidine (or placebo), 6 microg/kg orally 120 min before anesthesia and 3 microg/kg intravenously over 60 min before the end of surgery. The spontaneous baroreflex ("sequence") technique and analysis of heart rate variability were used to quantify control of heart rate at baseline, before induction of anesthesia, and 1 and 3 h postoperatively. RESULTS: Baroreflex slope and heart rate variability were reduced postoperatively in patients given placebo but not those given clonidine. Clonidine resulted in greater postoperative baroreflex slope and power at all frequency ranges compared with placebo (4.9+/-2.9 vs. 2.2+/-2.1 ms/mm Hg for baroreflex slope, 354+/-685 vs. 30+/-37 ms2/Hz for high frequency variability). Clonidine also resulted in lower concentrations of catecholamine, decreased mean heart rate and blood pressure, and decreased perioperative tachycardia and hypertension. CONCLUSIONS: Patients with hypertension exhibit reduced heart rate control during the recovery period after elective surgery. Clonidine prevents this reduction in heart rate control. This may represent a basis for the improved circulatory stability seen with perioperative administration of clonidine.

Effects of inhaled albuterol and ipratropium bromide on autonomic control of the cardiovascular system.

STUDY OBJECTIVE: Systemic administration of beta-agonist and anticholinergic drugs markedly impair normal autonomic heart rate control. The purpose of this study was to quantify and compare the effects of therapeutic doses of inhaled albuterol and ipratropium on autonomic control of the cardiovascular system. DESIGN: Randomized, double-blind, placebo-controlled, crossover design study. SETTING: Tertiary-care hospital. SUBJECTS: Twelve healthy male volunteers. INTERVENTIONS: Subjects self-administered four puffs through a spacer device from one of three identical inhalers containing albuterol (100 microg per puff), ipratropium (20 microg per puff), or placebo in three different testing sessions. MEASUREMENTS: ECG and noninvasive continuous BP traces were recorded at baseline and from 45 to 75 min after administration of the drug. Autonomic control of the cardiovascular system was quantified by analysis of spontaneous baroreflex sensitivity and power spectral analysis of heart rate variability. RESULTS: Neither albuterol nor ipratropium caused a significant alteration in baroreflex sensitivity, normalized low-power frequency, or normalized high-power frequency. No adverse effects were reported by subjects. CONCLUSIONS: Inhalation of four puffs of albuterol (400 microg) or ipratropium (80 microg) does not alter the autonomic control of the cardiovascular system in young, healthy male subjects.

The effects of reversal of neuromuscular blockade on autonomic control in the perioperative period.

Impaired parasympathetic control of heart rate is associated with increased incidence of cardiac dysrhythmias and ischemia. Anticholinergic drugs suppress parasympathetic control and could be detrimental in the early postoperative period in high-risk patients. In this double-blind randomized trial, 30 ASA physical status I and II patients undergoing minor surgery received either atropine 20 micrograms/kg and neostigmine 50 micrograms/kg (Group A), glycopyrrolate 8 micrograms/kg and neostigmine 50 micrograms/kg (Group G), or placebo (Group P) for reversal of neuromuscular blockade. Two indices of parasympathetic modulation of heart rate, spontaneous baroreflex sensitivity, and high-frequency heart rate variability, were assessed. At 2 h after reversal, Group A showed persisting impairment of baroreflex sensitivity with respect to Group P (7.12 +/- 0.86 vs 12.71 +/- 1.38 ms/mm Hg, P = 0.022) as well as decreased high-frequency heart rate variability (280.8 +/- 30.1 vs 569.2 +/- 115.2 ms2/Hz, P = 0.015). Groups A and G showed a borderline decrease in normalized high-frequency variability at 2 h (P = 0.05 for Groups A and G versus Group P). Anticholinergic drugs with neostigmine cause impairment of parasympathetic control of heart rate which persists into the early postoperative period. The effects of glycopyrrolate appear to be of shorter duration; this drug may thus be preferable in patients at risk of cardiovascular complications.

The duration of impairment of autonomic control after anticholinergic drug administration in humans.

Impaired parasympathetic control of heart rate is associated with increased incidence of cardiac dysrhythmias and ischemia. Anticholinergic drugs, commonly administered during reversal of neuromuscular blockade, suppress parasympathetic control in the early postoperative period. This could potentially be detrimental in patients at risk of cardiovascular complications. The duration of parasympathetic impairment by two anticholinergic drugs were compared in this double-blind randomized cross-over study. Fourteen healthy volunteers received a single intravenous injection of atropine 20 micrograms/kg or glycopyrrolate 8 micrograms/kg during two different study sessions. The methods of spontaneous baroreflex analysis and spectral analysis of heart rate variability generated indices of beat-by-beat parasympathetic modulation of heart rate. Both drugs resulted in a marked decrease in baroreflex sensitivity and high-frequency heart rate variability. The times to return to baseline values were approximately doubled after atropine compared to glycopyrrolate (177 +/- 22 vs 82 +/- 8 min for baroreflex sensitivity, 212 +/- 16 vs 111 +/- 14 min for high-frequency power, and 171 +/- 18 vs 95 +/- 18 min for high-frequency power normalized to total power; P < 0.01 for all variables). Atropine leads to more prolonged impairment of parasympathetic control than equipotent doses of glycopyrrolate, and its use may thus be less desirable in high-risk patients in the early postoperative period.

Reduction of post-operative nausea and vomiting with the combination of morphine and droperidol in patient-controlled analgesia.

PURPOSE: To determine whether low doses of droperidol mixed with morphine in patient-controlled analgesia (PCA) would extend the duration of prophylaxis against postoperative nausea and vomiting. METHODS: Healthy women having elective open-abdominal gynaecological surgery consented to this double-blind, placebo-controlled study. Subjects were randomized to receive placebo, or 1 mg droperidol before induction followed by droperidol 0.0 (bolus group), 0.02 (0.02 group), or 0.04 (0.04 group) mg.mg-1 of PCA morphine. Study endpoints included severity of nausea, episodes of vomiting and rescue antiemetic doses, pain, and sedation and were assessed at 1, 2, 4, 8, 12, 16, 20 and 24 hr postoperatively. RESULTS: Seventy-one subjects completed the study. The groups were similar in age, weight, surgical time, pain scores, and morphine used. The 0.04 group had lower mean visual analogue scale scores for nausea (P < 0.05 vs all other groups). The incidence of vomiting was lower in all treatment groups (P < 0.05 for all groups vs placebo). The 0.04 group had lower rescue antiemetic requirements than the bolus group (P < 0.03). Mean sedation scores were low in all groups but were increased with PCA droperidol (P < 0.02). CONCLUSIONS: Droperidol 1 mg before induction of anaesthesia reduces postoperative vomiting. The addition of droperidol 0.04 mg.mg-1 of PCA morphine further reduces (i) severity of nausea and (ii) rescue antiemetic requirements postoperatively. No clinically significant side-effects were attributed to this regimen.

Balloon flotation is more important than flow direction in determining the position of flow-directed pulmonary artery catheters.

Pulmonary artery catheters (PAC) inserted using pressure monitoring usually advance into a branch of the right pulmonary artery (PA). However, in some clinical situations it may be desirable to locate the tip of the PAC in a branch of the left PA. A two-part study was undertaken to explore factors that determine the ultimate location of the tip of a PAC. In the clinical study, 33 patients were randomized to supine or right-side down patient positioning during insertion of the PAC. Five patients were excluded because of withdrawal of the PAC during surgery. Seven of 14 PACs inserted in right-side down position were located in a branch of the left PA, while all 14 inserted with the patients supine went to a branch of the right PA (P less than 0.005). This suggests that the effect of upward flotation of the air-filled balloon in the column of blood predominates over movement with the current of maximal blood flow. Using a cardiac bypass pump and a plexiglass model of the pulmonary arterial bifurcation, the effects of lateral positioning on the direction of travel of balloon-tipped catheters were studied. The tip floated upward preferentially, even when flow was obstructed to the upward limb (P less than 0.005). Varying the flow rate in the system between 0.5 and 3.0 L/min and changing the direction of the natural curve of the PAC tip had no impact on this tendency to float upward. The authors conclude that balloon flotation in the column of blood strongly influences PAC tip location, and that this fact can assist in preferentially directing its placement.