Intramuscularly administered dexmedetomidine attenuates hemodynamic and stress hormone responses to gynecologic laparoscopy.

The hemodynamic and endocrine effects of three different doses of dexmedetomidine (0.6, 1.2, and 2.4 micrograms/kg), oxycodone (0.13 mg/kg), and saline solution, injected intramuscularly 45-60 min before induction of general anesthesia, were compared in a double-blind, randomized study involving 100 women undergoing gynecologic diagnostic laparoscopy. Anesthesia was induced with thiopental (4.5 mg/kg) and maintained with 0.3% end-tidal isoflurane and 70% nitrous oxide in oxygen. Arterial blood pressure and heart rate increased after endotracheal intubation and during laparoscopy in all groups, but the maximal mean arterial pressure after tracheal intubation was lower in the dexmedetomidine 2.4-micrograms/kg group (104 mm Hg [SD 19]) than in the saline solution group (130 mm Hg [SD 12]). Dexmedetomidine (2.4 and 1.2 micrograms/kg) attenuated the maximal heart rate after intubation (84 [SD 11] and 101 beats/min [SD 15], respectively) compared with saline solution (116 beats/min [SD 19]). On the other hand, 40% of the patients in the dexmedetomidine 2.4-micrograms/kg group received atropine in the postanesthesia care unit for bradycardia (heart rate < or = 40 beats/min). Preoperative anxiety and sedation before and after preanesthetic medication were evaluated by the patients with the aid of a profile of mood-state questionnaire; only dexmedetomidine 2.4 micrograms/kg produced significant anxiolysis and sedation. Plasma concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylglycol, cortisol, and beta-endorphin increased less in the dexmedetomidine 2.4-micrograms/kg group in response to tracheal intubation and surgery than in the saline solution group.

Nausea and vomiting after gynaecological laparoscopy depends upon the phase of the menstrual cycle.

Postoperative nausea and vomiting were compared in 68 women with regular menstrual periods undergoing gynaecological laparoscopy. The patients were divided into four group on the basis of the phase of the menstrual cycle as follows: premenstrum-menstrum (pre + menstrum) (Pd 25-6), early follicular phase (Pd 8-12), ovulatory phase (Pd 13-15) and luteal phase (Pd 20-24). The overall incidence of nausea and vomiting was 46%. Statistically significant differences in the incidence of nausea and retching were found among the groups by regression analysis. The incidence of nausea and vomiting was highest in women undergoing laparoscopy during the luteal phase (77%), which was greater than during the follicular phase (32%) or during pre + menstruation (18%). The need for antimetic was highest in women undergoing laparoscopy during the luteal phase (69%) and this was different from the follicular (18%, P less than 0.01) and pre + menstrum (19%, P less than 0.01) phases. It is concluded that the highest incidence of postoperative nausea and vomiting after gynaecological laparoscopy occurs during the luteal phase.

Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation.

Ninety-six women undergoing laparoscopic tubal ligation were randomized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine, 60 micrograms/kg of oxycodone, or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design. The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared. In the group receiving diclofenac, 83% of the patients required analgesic supplementation with morphine. This contrasted (P less than 0.01) with 33% of the patients receiving either oxycodone or the higher dose of dexmedetomidine. After the first dose of oxycodone was injected, the visual analogue scale for pain (0%-100%) was reduced from 58% to 33%, whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine. Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17%. More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone (P less than 0.001). Both doses of dexmedetomidine decreased heart rate when compared with diclofenac (P less than 0.001). In the group given 0.4 microgram/kg of dexmedetomidine, 33% of the patients required atropine for bradycardia. The authors conclude that after laparoscopic tubal ligation, intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia.

The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy.

The effects of two doses of dexmedetomidine (0.3 or 0.6 micrograms.kg-1), fentanyl 2.0 micrograms.kg-1, or saline as a single intravenous bolus administered 10 min prior to the induction of anesthesia were assessed in double-blind, randomized study in 96 women undergoing abdominal hysterectomy. In each patient, anesthesia was induced with thiopental 4.0 mg.kg-1, and after the effect of succinylcholine had dissipated, isoflurane 0.3% end-tidal concentration in 70% nitrous oxide was begun to maintain anesthesia. The isoflurane concentration was adjusted to maintain blood pressure and heart rate within 20% of preoperative values, and fentanyl was given if the end-tidal isoflurane concentration exceeded 1.5%. In all groups, blood pressure and heart rate increased after tracheal intubation. However, the increase in blood pressure and heart rate was significantly less in the higher dexmedetomidine (0.6 micrograms.kg-1) group than in the saline group (P less than 0.01). Also, the postintubation increase in heart rate was significantly less (P less than 0.05) in the dexmedetomidine 0.6 micrograms.kg-1 group (increase of 18 +/- 3 beats per min) compared to the fentanyl group (increase of 26 +/- 3 beats per min). In patients receiving dexmedetomidine 0.3 micrograms.kg-1, the increase in blood pressure or heart rate did not differ from that of the saline group. The mean end-tidal isoflurane concentration was significantly less in the women receiving the higher dose of dexmedetomidine (0.35%) than in those receiving saline (0.47%) or fentanyl (0.48%), although the reduction was not clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of orally administered diazepam and midazolam on plasma beta-endorphin, ACTH and preoperative anxiety.

Ninety-five women undergoing induced abortion were randomly premedicated with oral diazepam, 5 or 10 mg, midazolam 15 mg, or intramuscular placebo, 40-60 min before the induction of anesthesia. Prior to premedication and again prior to the procedure, the women completed the questionnaire sheet for the Profile of Mood States (POMS), and plasma samples for immunoreactive beta-endorphin (ir beta-E) and ACTH were taken. The Oblique Tension-Anxiety (T-A) Factor scores derived from POMS correlated with plasma concentrations of ir beta-E and ACTH after premedication. The T-A scores decreased in women premedicated with diazepam, 5 and 10 mg, or midazolam, 15 mg, but not in women treated with placebo. The women premedicated with midazolam, 15 mg, became more fatigued after premedication. The changes in blood pressure after premedication correlated with T-A scores. A positive correlation was found between heart rate and plasma beta-endorphin concentration. The changes in ir beta-E and ACTH did not correlate with the changes in T-A scores. We conclude that POMS T-A scores are useful for assessment of preoperative anxiety and the effect of premedication. The present study did not provide any reliable proof to confirm the hypothesis of a relationship between plasma concentrations of ir beta-E or ACTH and preoperative anxiety. Since many factors modulate endorphin and ACTH secretion prior to operation, the measurement of endogenous opiates may be of limited value in assessment of the effects of preanesthetic medication.

Effects of intramuscular clonidine on hemodynamic and plasma beta-endorphin responses to gynecologic laparoscopy.

Ninety women undergoing gynecologic laparoscopy were randomly given clonidine 3 or 4.5 micrograms/kg or saline intramuscularly 45-60 min prior to induction of anesthesia. Anesthesia was induced with thiopental 3.5 mg/kg and maintained with 0.3% end-tidal isoflurane in nitrous oxide and oxygen. The laparoscopy did not begin sooner than 20 min after tracheal intubation. Arterial blood pressure and heart rate were monitored with an automatic oscillometer. When compared with the baseline values, clonidine 4.5 micrograms/kg significantly (P less than 0.001) decreased the mean arterial pressure (MAP) measured before induction of anesthesia. In all three groups, blood pressure and heart rate increased after tracheal intubation and after beginning of laparoscopy (P less than 0.001), but the increments were significantly greater in the control group than in the study groups. During anesthesia alone without surgical stimulation, and again in the recovery room, MAP and heart rate were lower in the study groups than in the control group. Plasma beta-endorphin immunoreactivity (ir beta-E) was measured for ten control-group women and ten women receiving clonidine 4.5 micrograms/kg before premedication, before and after induction of anesthesia, during laparoscopy, and 1 h after the procedure. The plasma ir beta-E increased significantly after the beginning of laparoscopy in both the control group and those given clonidine, but the increase was significantly less (P less than 0.05) in the women premedicated with clonidine. The blunting effect of clonidine on hemodynamics and plasma beta endorphin may reflect a deeper level of anesthesia in those women receiving clonidine as preanesthetic medication or can be explained by an interaction of clonidine with endogenous opiates. The authors conclude that intramuscularly administered clonidine premedication effectively prevents the maximal hemodynamic responses to tracheal intubation and to gynecologic laparoscopy. Further clinical studies on the clinical importance of the role of clonidine preanesthetic medication are warranted.

Modifying effects of epidural analgesia or general anesthesia on the stress hormone response to laparoscopy for in vitro fertilization.

Modifying effects of epidural analgesia and general anesthesia on stress hormone release was studied during laparoscopy for in vitro fertilization (IVF). In 24 women follicle development was stimulated by clomiphene and gonadotropin treatment, and oocytes were collected by laparoscopy under epidural analgesia in 11 women and under fentanyl-supplemented nitrous oxide-oxygen anesthesia in 13. The plasma levels of immunoreactive beta-endorphin (ir beta-E), cortisol, and prolactin (PRL) did not change under epidural analgesia per se, but after the start of laparoscopy, increased release of all these stress hormones was observed. General anesthesia per se increased the release of PRL, whereas the release of cortisol and ir beta-E decreased, probably due to the effects of fentanyl and thiopentone. During the stress attributed to laparoscopy, significantly more ir beta-E and cortisol was released under epidural than under general anesthesia, whereas the release of PRL was more significant under general anesthesia. These results show that neither mode of anesthesia prevented the stress response to laparoscopy. In the subsequent midluteal phase, the mean plasma level of progesterone and the mean progesterone-estradiol ratio were significantly greater in the epidural than in the general anesthesia group, suggesting that the mode of anesthesia may have an effect on the luteal phase. The significance of this difference on the conception rate remained unsolved, however.

Continuous infusion of fentanyl or alfentanil for coronary artery surgery. Effects on plasma cortisol concentration, beta-endorphin immunoreactivity and arginine vasopressin.

Plasma cortisol, beta-endorphin immunoreactivity (PBEir) and arginine vasopressin (AVP) responses during and after the continuous infusion of fentanyl or alfentanil were studied in 19 patients undergoing coronary artery bypass grafting (CABG). Plasma cortisol concentration decreased significantly in both groups during the anaesthesia and surgery before cardiopulmonary bypass (CPB); an increase was evident during CPB in both groups, but a statistically significant increase was not observed during the rest of the study, including the awakening from anaesthesia. PBEir increased with both opiates immediately after initiation of CPB and remained so during the rest of the study. There were no significant changes in plasma AVP concentrations during anaesthesia and surgery. After discontinuation of opiate infusions, an increase in AVP concentration commenced earlier in the alfentanil group than in the fentanyl group. At awakening from anaesthesia, a significant correlation was observed between log plasma AVP concentration and systemic vascular resistance. It is concluded that, with continuous fentanyl and alfentanil infusions in a total dose relationship of 1:13 in patients undergoing CABG, cortisol and AVP responses to surgery and CPB can be suppressed. However, during recovery from anaesthesia, the attenuating effect of alfentanil seems to wear off more rapidly than that of fentanyl. PBEir response to CPB and emergence from anaesthesia could not be prevented with either analgesic.

The effect of anaesthesia on changes in blood pressure and plasma cortisol levels induced by cementation with methylmethacrylate.

The effects of cementation on arterial blood pressure, arterial oxygen tension and plasma levels of cortisol were studied in 30 patients with femoral neck fracture treated with the Thompson prosthesis in spinal (n = 15) or general (n = 15) anaesthesia. In spinal anaesthesia hypotension of clinical importance was observed coincidentally with the use of methylmethacrylate, while the levels of plasma cortisol remained unchanged. A significant rise was noted in arterial blood pressure and plasma levels of cortisol after cementation in general anaesthesia. Arterial oxygen tension fell in both groups. These findings indicate that the hypotension frequently reported in connection with cementation is triggered by a complex mechanism which can be modified by the anaesthetic technique.

Comparison of alfentanil and fentanyl as supplements to induction of anaesthesia with thiopentone.

In 120 premedicated patients undergoing general surgery, anaesthesia was induced with thiopentone 3 mg kg-1, preceded by alfentanil 4.5, 9.0 or 13.5 micrograms kg-1 or fentanyl 1.5 micrograms kg-1. The largest alfentanil dose attenuated the arterial blood pressure response to laryngoscopy and intubation better than the smaller doses of alfentanil. Changes in frontal muscle electromyogram or plasma cortisol and prolactin levels were not dependent on the adjuvant used. After thiopentone, 30, 7 and 17% of the patients given alfentanil 9.0 and 13.5 micrograms kg-1 and fentanyl 1.5 micrograms kg-1, respectively, reacted to pinching of the lower abdomen. Patients given alfentanil 4.5 micrograms kg-1 did not tolerate the endotracheal tube after recovery from suxamethonium block and their heart rate was increased 12 min after alfentanil administration. We conclude that the antinociceptive effect of alfentanil is distinctly shorter than that of fentanyl. The analgesic potency of alfentanil is between one sixth and one ninth of that of fentanyl.

Modification of aspects of the endocrine response to tracheal intubation by lignocaine, halothane and thiopentone.

The effects of two different concentrations of halothane (0.5 or 1.5%) and two different doses of thiopentone (4.5 or 10 mg kg-1) on the plasma concentrations of cortisol, growth hormone (GH) and prolactin (PRL) were studied in response to the stress of tracheal intubation. Additionally, the effect of the intratracheal administration of 4% lignocaine spray 2 ml was investigated. The study group included 48 healthy women. During a "light" level of halothane and thiopentone anaesthesia, the plasma concentration of cortisol increased in response to tracheal intubation in the patients who did not receive intratracheal analgesia. Topical analgesia with lignocaine prevented the increase in cortisol concentration and this would seem to indicate that the increase was caused by the stress of laryngoscopy and intubation. At a deeper level of halothane anaesthesia, and in association with the larger dose of thiopentone the increase in cortisol concentration was suppressed. GH did not change from the preanaesthetic value in any group and there were no differences between the control group and the study groups. PRL increased significantly in all groups. Increasing the dose of thiopentone caused a further increase in PRL concentration which indicated a direct stimulatory action of thiopentone on PRL release.

Effect of intratracheal lignocaine, halothane and thiopentone on changes in plasma beta-endorphin immunoreactivity in response to tracheal intubation.

Alterations in the concentration of plasma beta-endorphin immunoreactivity (beta-EPir), in response to the stress of tracheal intubation, were measured in 48 women during halothane anaesthesia. The increase in plasma beta-EPir in response to tracheal intubation could be prevented by topical analgesia (4% lignocaine 2 ml) to the trachea, a deeper level of halothane anaesthesia (1.5%) and an increased dose of thiopentone (10 mg kg-1). It was concluded that a low plasma beta-EPir value is a sign of stress-free anaesthesia and that measurements of plasma beta-EPir may be useful in determining the degree of stress present during various anaesthetic procedures.

The effect of fentanyl on arginine vasopressin and cortisol secretion during anesthesia.

The effects of nitrous oxide-oxygen plus small doses of fentanyl with (N = 7) and without (N = 15) naloxone and the effects of nitrous oxide-oxygen plus halothane (N = 13) on plasma concentration of arginine vasopressin (AVP) and cortisol were studied in normal patients before and during gynecologic laparotomies. Patients given fentanyl alone received incremental doses of 0.002 mg/kg before, during, and after induction of anesthesia. Naloxone, when given, was injected in doses of 0.005 mg/kg before administration of fentanyl. In the fentanyl group, the induction of anesthesia resulted in a significant increase in the plasma AVP levels and a significant decrease in cortisol levels. In contrast, while the halothane group also showed a decrease in plasma cortisol level, there was no change in the AVP levels. There were comparable increases in AVP and cortisol levels in both groups during surgery. Administration of naloxone before fentanyl prevented the increase of plasma AVP levels during anesthesia and surgery and blunted the elevation of plasma cortisol during surgery. Our results suggest that the increase in plasma AVP levels after induction of fentanyl anesthesia may not be induced by the stress of intubation and that small doses of fentanyl may cause AVP release during anesthesia.

Recovery after general anaesthesia for laparoscopy.

Recovery after two methods of light general anaesthesia for gynaecological laparoscopy was studied. For this purpose, 30 patients were divided into two equal groups (A and B). The patients in group A were anaesthetized with thiopentone, fentanyl and suxamethonium infusion, while the patients in group B received inhalation anaesthesia with enflurane and suxamethonium infusion. Both groups were normoventilated with nitrous-oxide and oxygen mixture. A battery of recovery tests was applied in the recovery room. The patients who received inhalation anaesthesia with enflurane scored better in the recovery tests, and reached preoperative values after 3 h in the recovery room. Inhalation anaesthesia with enflurane was accepted well by the patients and provided good working conditions for the surgeons. It is suitable for outpatient gynaecological laparoscopy because it ensures rapid recovery.