Pulmonary vascular effects of propofol at baseline, during elevated vasomotor tone, and in response to sympathetic alpha- and beta-adrenoreceptor activation.

BACKGROUND: This in vivo study had two primary objectives. The first goal was to determine whether the pulmonary vascular effects of propofol depend on the preexisting level of vasomotor tone, and the second was to investigate the effects of propofol on the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation. METHODS: Thirty-one mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relation. Left lung autotransplantation (LLA) was also performed in eight additional dogs to induce a long-term increase in pulmonary vascular resistance. LPQ plots were measured on separate days in the conscious state and during propofol anesthesia. LPQ plots were measured at baseline and when vasomotor tone was acutely increased with the alpha agonist, phenylephrine, or the thromboxane mimetic, U46619. In separate experiments, cumulative dose-response curves to alpha- (phenylephrine) and beta- (isoproterenol) adrenoreceptor agonists were generated in conscious and propofol-anesthetized dogs. RESULTS: Compared with the conscious state, propofol had no effect on the baseline LPQ relation in normal or post-LLA dogs. However, propofol caused pulmonary vasoconstriction (P < 0.05) when vasomotor tone was acutely increased with either phenylephrine or U46619 in normal or post-LLA dogs. The pulmonary vasoconstrictor response to alpha-adrenoreceptor activation was potentiated (P < 0.05) during propofol anesthesia, whereas the pulmonary vasodilator response to beta-adrenoreceptor activation was not altered. CONCLUSION: These results indicate that the pulmonary vascular response to propofol anesthesia is tone-dependent. During sympathetic activation, propofol may favor alpha-adrenoreceptor-mediated vasoconstriction over beta-adrenoreceptor-mediated vasodilation.

Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in chronically instrumented dogs.

BACKGROUND: The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state. METHODS: Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators. RESULTS: Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation. CONCLUSION: These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.

[Hemorrhage exerts different effects on variabilities of heart rate and blood pressure in dogs].

The aim of the present study was to evaluate the effects of hemorrhage on heart rate variability (HRV) and blood pressure variability (BPV) as indicators of autonomic nervous system (ANS) and hypovolemia. We induced hemorrhagic hypovolemia in 7 dogs by removing blood in graded stages (0%, 10%, 20%, 30%, 40% of the estimated blood volume; EBV). HR was unchanged during hemorrhage, while mean BP decreased significantly after 30% EBV hemorrhage. Low frequency component (LF: 0.04-0.15 Hz) of HRV significantly increased after 20% EBV hemorrhage but high frequency component (HF: 0.15-0.4 Hz) of HRV was not altered. LF of BPV increased significantly stepwise after 20% EBV hemorrhage and HF of BPV increased significantly after 30% EBV hemorrhage, showing that both LF and HF of BPV might indicate the degree of hypovolemia. During hemorrhage LF of HRV and BPV increased and HF of HRV was unchanged, indicating the shift of the autonomic balance toward sympathetic dominance. An excellent quantitative correlation between LF of BPV and the degree of hypovolemia was demonstrated during graded hemorrhage, while LF of HRV plateaued at its maximum value at 20% EBV hemorrhage. In conclusion, our study suggests that the spectral analysis of HRV and BPV during graded hemorrhage shows different characteristics in the quantitative evaluation of ANS and hypovolemia.

Pulmonary vasodilator response to adenosine triphosphate-sensitive potassium channel activation is attenuated during desflurane but preserved during sevoflurane anesthesia compared with the conscious state.

BACKGROUND: The objective of this study was to investigate the effects of sevoflurane and desflurane anesthesia on the pulmonary vasodilator response to the adenosine triphosphate-sensitive potassium channel agonist, lemakalim, compared with the response measured in the conscious state. In addition, the authors assessed the extent to which sympathetic alpha1-adrenoreceptor inhibition and cyclooxygenase pathway inhibition modulate the vasodilator response to lemakalim. METHODS: Twenty-four conditioned male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow relationship. After preconstriction with the thromboxane analogue, U46619, dose-response relationships to lemakalim were assessed on separate days in the conscious state and during sevoflurane (approximately 3.5% end-tidal) and desflurane (approximately 10.5% end-tidal) anesthesia (approximately 1.5 minimum alveolar concentration for each anesthetic agent). The effects of sympathetic alpha1-adrenoreceptor inhibition (prazosin) and cyclooxygenase inhibition (indomethacin) on the pulmonary vasodilator response to lemakalim also were assessed in the conscious and desflurane-anesthetized states. RESULTS: Neither sevoflurane nor desflurane had a net effect on the baseline left pulmonary vascular pressure-flow relationship compared with the conscious state. The magnitude of the pulmonary vasodilator response to lemakalim was preserved during sevoflurane anesthesia but was attenuated (P < 0.05) during desflurane anesthesia compared with the conscious state. The attenuated lemakalim-induced vasodilator response during desflurane anesthesia was partially reversed (P < 0.05) by pretreatment with prazosin but not indomethacin. CONCLUSION: These results indicate that adenosine triphosphate-sensitive potassium channel-mediated pulmonary vasodilation is preserved during sevoflurane anesthesia but is attenuated during desflurane anesthesia. The attenuated response to adenosine triphosphate-sensitive potassium channel activation during desflurane anesthesia is partially mediated by reflex sympathetic alpha1-adrenoreceptor vasoconstriction.

[Continuous epidural morphine for postoperative pain relief after spinal surgery--use of an epidural catheter placed at the time of surgery].

Postoperative analgesia by continuous epidural morphine infusion after spinal surgery was investigated in a retrospective study. An epidural catheter was placed by surgeons at the time of surgery. Postoperative pain was less intense and use of analgesics and sedative was less frequent in patients with continuous epidural morphine (n = 41) as compared with patients without continuous epidural morphine (n = 41). Among the patients with continuous epidural morphine, postoperative pain in patients (n = 16) with the dura opened or dural rent during surgery was less intense and the uses of analgesics and sedative was less frequent as compared with patients (n = 25) without the dural rent. There were no severe complications except for respiratory depression in a patient with chronic obstructive pulmonary disease. Our study demonstrated the ease of insertion of an epidural catheter at the time of surgery and the good quality of epidural analgesia after spinal surgery.

[Effects of prostaglandin E1 on temperature gradients between hand and foot during epidural anesthesia].

We studied the effects of prostaglandin E1 (PGE1) on hand-foot temperature gradients (foot temperature-hand temperature) induced by lumbar epidural anesthesia. Thirty-six ASA class 1 patients undergoing rotatory acetabular osteotomy were randomly assigned to receive 0 gamma (n = 13), 0.005 gamma (n = 10) and 0.02 gamma (n = 13) of PGE1. Thermometric probes were placed on the palm and sole of each patient. Bladder temperature was also monitored to evaluate the change of core temperature. Epidural catheter was indwelled at the level between L2 and L3 prior to induction and 2 % lidocaine was administered epidurally. All patients were warmed by water blanket at 37 degrees C and fluids for infusion warmed at 37 degrees C. Humidity and moisture exchanger was placed in breathing circuit. Hand-foot temperature gradients of patients given 0 and 0.005 gamma of PGE1 increased to 2.8 +/- 1.5 and 2.3 +/- 2.3 degrees C at extubation, respectively. In contrast, temperature gradient of patients given 0.02 gamma of PGE1 was 0.0 +/- 1.8 degrees C (P < 0.01). There was no difference among the values of bladder temperature in each group. The effects of PGE1 on mean arterial pressure, heart rate and central venous pressure were minimal. These data suggest that 0.02 gamma of PGE1 administration is effective to reduce hand-foot temperature gradient during epidural anesthesia.

[Effects of prostaglandin E1 on renal function during deliberate hypotension with epidural anesthesia].

We studied the effects of prostaglandin E1 (PGE1) on renal function during and after deliberate hypotension induced by epidural anesthesia. Twenty-seven ASA class 1 patients undergoing rotatory acetabular osteotomy were divided into three groups according to the dose of PGE1. Deliberate hypotension was induced and maintained during the surgery by epidural anesthesia combined with general anesthesia. PGE1 increased urine output and creatinine clearance (Ccr) during hypotension in dose dependent manner, and the changes were statistically significant compared with control at the dose of 0.02 micrograms.kg-1 x min-1 (gamma). PGE1 also tended to increase postoperative urine output and Ccr. Regardless of PGE1 administration, urine NAG/Cr ratio tended to increase during and after deliberate hypotension. Though total dose of local anesthetics was attenuated by PGE1, serum catecholamine levels of all patients were within normal ranges. In conclusion, PGE1 0.02 gamma is effective to maintain urine output during deliberate hypotension with epidural anesthesia. However, PGE1 is unlikely to prevent renal tubular damage at the dose less than 0.02 gamma.

[Effect of combined spinal and epidural anesthesia on blood loss during total hip replacement].

Ninety total hip replacements (THRs) performed by one surgeon were reviewed to compare the effects of different anesthetic techniques on the perioperative bleeding. Half of the THRs were performed under either combined spinal and epidural (CSE) anesthesia with lidocaine or general anesthesia with N2O/O2, vecuronium, enflurane or isoflurane. Deliberate hypotensive technique was not employed in any THR. All patients were female and had suffered from osteoarthritis of the hip joints. The patients in the two anesthesia groups were similar as to age, body weight, height, perioperative hemoglobin level, duration of anesthesia and operation, and blood transfusion requirement. A positive linear correlation existed between total operative blood loss and operation time in each group (P < 0.01). The rate of operative blood loss was significantly higher in the CSE anesthesia (6.2 +/- 3.0 ml.min-1) than in the general anesthesia (5.1 +/- 2.0 ml.min-1), while the amount of blood loss itself was without statistical difference. A significant increase in total volume of perioperative blood loss was also observed in the group with CSE anesthesia (1520 +/- 90 ml) compared with the general anesthesia group (1279 +/- 58 ml). These results show that spinal and/or epidural anesthesia can not always lead to reductions in operative blood loss during THR.

[Anesthetic problems in patients with Forestier's disease].

We have studied common problems associated with the anesthetic management of Forestier's disease in 8 patients undergoing neurosurgery. This disease is a systemic degenerative disorder and is characterized by osteo-spur formation at anterior spinal body. In two of eight patients the trachea was intubated with great difficulty even by well-trained anesthesiologist. Its cause could be found not only in limited cervical mobility but also in constrained epiglottic elevation, suggesting that Forestier's disease requires special anesthetic considerations. It is thus important to predict the possibility of difficult tracheal intubation on both physical examination and the preoperative X-ray photography.

[The catecholamine concentrations of collected autologous blood during adrenalectomy for pheochromocytoma].

We have studied the concentrations of catecholamines in collected autologous blood. The measured levels of the blood samples from Cell-stat collecting chamber were epinephrine 4.74 ng.ml-1 and norepinephrine 2.39 ng.ml-1. First wash of collected blood with 700 ml of saline diluted the catecholamine concentrations to epinephrine 3.13 ng.ml-1 and norepinephrine 1.6 ng.ml-1. The concentrations of catecholamines after second wash were epinephrine 2.19 ng.ml-1 and norepinephrine 1.11 ng.ml-1. These values were three to twenty folds of normal ranges even after the second wash, and still the same levels as intraoperative plasma catecholamine (the measured values; epinephrine 0.81-2.81 ng.ml-1 and norepinephrine 0.96-3.15 ng.ml-1). Since platelets actively concentrate catecholamines during their life span, the destruction of platelets by suction or centrifugation may probably play the most important role in the elevation of catecholamine concentrations in the collected autologous blood. We concluded that intraoperative autotransfusion in the resection of pheochromocytoma is likely to result in the elevation of systemic blood pressure by catecholamines of the transfused blood.

[Combined spinal and epidural anesthesia for orthopaedic surgery in the elderly].

The pros and cons as to which anesthesia is more beneficial, either spinal or epidural, prompted us to perform combined spinal and epidural block in the elderly undergoing lower limb surgery. The selected epidural space was entered with a 17-gauge Tuohy needle and a longer 26-gauge spinal needle was passed through it and into the subarachnoid space. Following the injection of required dose of 2% preservative-free lidocaine (isobaric), spinal needle was withdrawn and an epidural catheter was inserted. We could use this combined technique on 17 patients older than 80 yr (mean age; 84.5 +/- 3.9 years) with satisfactory results and without any serious cardiovascular change, as with 17 middle-aged patients (57.5 +/- 5.2 years). This combination of techniques provides a rapid onset and reliability of spinal block with high quality analgesia by supplementation through the epidural catheter during and after surgery. In the orthopaedic procedures on the lower limbs, combined spinal and epidural block is more useful even for the elderly over the age of 80 yr than spinal or epidural anesthesia alone.

[The effect of glucose loading on changes in ketone and glucose metabolism during gastrectomy].

Plasma glucose, insulin, glucagon, free fatty acid, ketone body, lactate and pyruvate were measured in 14 patients undergoing gastrectomy under general anesthesia with nitrous oxide and oxygen. Lactated ringer solution with glucose load (10 g.hr-1) was administered in seven patients [glucose loading group: Glucose (+)] and the other seven patients received only lactated ringer solution [glucose free group: Glucose (-)]. Blood glucose increased significantly in both groups, but a significant difference appeared between Glucose (+) and Glucose (-). Plasma insulin activity and IRI/BS ratio increased in Glucose (+) and a significant difference was found between the two groups. No remarkable change in plasma glucagon level was found in both groups. Free fatty acid and ketone bodies (acetoacetate, beta-hydroxybutyrate) decreased significantly in Glucose (+), but they increased significantly in Glucose (-) and significant differences were found between the two groups. The rate of changes of beta-hydroxybutyrate was consistently higher than that of acetoacetate. Lactate and pyruvate increased significantly in both groups. These results suggest that continuous glucose loading may facilitate insulin release from the pancreas and suppress the hyperketonemia and hyperlipidemia during partial gastrectomy.