The anesthetic management of triplet cesarean delivery: a retrospective case series of maternal outcomes.

UNLABELLED: Spinal anesthesia for the cesarean delivery of triplets is associated with an increased incidence of maternal hypotension and placental hypoperfusion. We performed a retrospective case series analysis between January 1992 and June 2000 to evaluate the effects of regional anesthetic techniques for cesarean delivery in triplet pregnancies on maternal and neonatal outcome. Spinal and epidural anesthesia were compared with respect to intraoperative hemodynamics and neonatal outcomes. Ninety-six triplet pregnancies were delivered by cesarean section, of which 91 received regional anesthesia. A statistically significant decrease in systolic blood pressure was demonstrated immediately after the induction of spinal as compared with epidural anesthesia. The total volume of IV crystalloid used was significantly larger in the Spinal Anesthesia group. The number of patients receiving more than 15 mg of ephedrine and the cumulative dose of ephedrine was significantly larger in the Spinal group compared with the Epidural group. There were no differences in the rate of perioperative complications between the Spinal and Epidural Anesthesia groups. Neonatal Apgar scores were similar in both groups. The data suggest that both epidural and spinal anesthesia for triplet cesarean delivery are safe techniques, but the latter is associated with a larger initial decrease in systolic blood pressure. This decreasing of systolic blood pressure, however, remained within the physiological range and did not seem to be clinically significant. The need for more crystalloid fluids and ephedrine should be anticipated when spinal anesthesia is used for these cases. IMPLICATIONS: A large retrospective case series of the effects of spinal and epidural anesthesia on maternal hemodynamic profile during cesarean delivery for triplet gestation was performed. Our findings suggest that spinal anesthesia results in outcomes comparable to epidural anesthesia for both mother and newborns.

Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain.

UNLABELLED: Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cistemal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. IMPLICATIONS: We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

Acute pain.

Postanaesthesia care units used to echo with cries of patients in pain after general anaesthesia. Each as-needed dose of analgesia was given only after permission of the surgeon or anaesthesiologist. Once conscious, patients were required to request each subsequent analgesic dose until hospital discharge. Not surprisingly, nearly half the patients who have an operation experience moderate to severe pain after surgery. Acute pain control has advanced dramatically and is now a field with dedicated texts, journals, and research. Despite improved surgical techniques that have transformed many operations into same-day procedures, inadequately controlled pain may still extend the length of hospital stay and predispose to expensive, time-consuming complications such as pneumonia. Recognition of economic and humanitarian benefits of pain control has prompted worldwide attention from professional groups, insurers, and governments. This paper describes the process of acute pain and measures to control it with drugs or non-pharmacological interventions. Even brief intervals of acute pain can induce long-term neuronal remodelling and sensitisation ("plasticity"), chronic pain, and lasting psychologial distress. Hence, acute pain and other types of pain (cancer-related or chronic) that are classified as distinct actually have many similarities.

Differential effect of central versus parenteral administration of morphine sulfate on regional concentrations of reduced glutathione in rat brain.

Prior studies in rodents have shown significant depletion of reduced glutathione (GSH) in peripheral organs following acute systemic or central administration of opioids. However, little information exists on whether opioid administration affects concentrations of brain GSH. Recently, clinical observations have indicated acute declines of GSH concentrations in the cerebrospinal fluid of cancer patients after acute intracerebroventricular (ICV) morphine which may contribute to the development of organic behavioral brain syndromes associated with central opioid analgesia. Collectively these data led us to investigate the affect of acute systemic and central morphine on regional concentrations of GSH in rat brain. Systemic morphine had no effect on GSH concentrations in selected brain areas. In contrast, ICV morphine resulted in selective GSH depletion in the caudate nucleus, consistent with concurrent excitatory locomotive behavior. This change may have reflected morphine-induced oxidative stress together with increased metabolic activity within the extrapyramidal system.

Evaluation of the effects of autotransfusion of unprocessed blood on hemodynamics and oxygen transport in anesthetized pigs.

OBJECTIVE: To examine the hemodynamic effects and the oxygen transport pattern of autotransfusion of unprocessed blood on hemodynamics and oxygen transportation. DESIGN: Prospective, observational study. SETTING: Research laboratory of a university medical center. SUBJECTS: Six healthy, domestic pigs (20 - 33 kg). INTERVENTIONS: A left thoracotomy was performed and a 5-mm incision was created in the descending aorta, resulting in a controlled hemorrhage of 30 mL/kg (approximately 40% of blood volume) into the thoracic cavity over a 45-min time period. During that period, mean arterial pressure (MAP) was maintained slightly > 50 mm Hg, using intravenous lactated Ringers' solution. The blood sample was collected from the open thorax with compresses soaked in citric acid solution and then extracted by manual squeezing, filtered through several layers of gauzes, and stored in glass bottles. Repeat measurements were performed after hemorrhage, after retransfusion of the harvested blood, and thereafter every 15 mins up to 60 mins. The animals were supported for 2 more hrs and were observed for the following 48 hrs. MEASUREMENTS AND MAIN RESULTS: All animals survived and were in good condition 48 hrs after the experimental hemorrhage. The circulatory and oxygen transport response at the end of hemorrhage and concomitant maintenance of blood pressure at > 50 mm Hg resulted in: significant reductions of cardiac index, MAP, and oxygen transport (DO2) (46%, 50%, and 64% reductions, respectively, p < .01, in an increase of heart rate (HR) (+21%, not significant), pulmonary vascular resistance index (+112%, p < .05), and oxygen extraction (+105%, p < .01), as well as in a nonsignificant decrease of systemic vascular resistance index (-8%). After autotransfusion, the basic hemodynamic variables, MAP and HR were corrected, remaining near baseline (not significant) afterward. Cardiac index and DO2 increased after autotransfusion, but remained below the baseline until the end of the study protocol (p < .05). A significant increase was noticed for pulmonary arterial pressure and pulmonary vascular resistance index immediately after autotransfusion (p < .01). These values were corrected in part after 15 to 30 mins, but remained higher throughout the observaton period compared with baseline (29.5% and 89.8%, respectively, p < .05). The recently introduced relationship between cardiac index and oxygen extraction has been proposed to avoid problems of mathematical coupling between oxygen consumption and DO2 measurements. This relationship followed a similar course in all experiments throughout each phase. A shift downward and to the right represented the endpoint of the hemorrhagic phase. After autotransfusion, a shift toward baseline was noticed. Prothrombin time and partial thromboplastin time remained unchanged after autotransfusion. Free hemoglobin concentrations increased immediately after autotransfusion (+33%, p < .05), but returned to baseline values 48 hrs later. Histologic examination showed no changes in the examined organs. CONCLUSIONS: Reinfusion of large amounts of unprocessed blood (up to 40% of blood volume), collected with compresses from a noncontaminated surgical field is a cheap method, which may be of potential benefit in trauma patients, when more sophisticated autotransfusion devices are lacking. In the present study, this method resulted in transient but significant hemodynamic changes in the pulmonary circulation. Impairment of oxygen transport was noticed after the end of hemorrhage, but this impairment cannot be attributed to the autotransfusion technique alone, but also to factors such as hemorrhagic shock, surgical trauma, etc.

Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose-response study.

BACKGROUND: Epidural clonidine produces effective postoperative analgesia in humans. Observed side effects include hypotension, bradycardia, sedation, and dryness of the mouth. A recent clinical study demonstrated that 150 micrograms intrathecal clonidine administered postoperatively as the sole analgesic agent was effective but produced hypotension and sedation. Animal studies have provided evidence of a biphasic effect on blood pressure after intrathecal clonidine administration, but no data concerning this effect in humans currently exist. This study was performed to evaluate the dose-response hemodynamic and analgesic profiles of intrathecal clonidine administered after a standard surgical intervention, without perioperative administration of additional analgesics, local anesthetics, or tranquilizers. METHODS: In a randomized prospective double-blind study, 30 women who underwent elective cesarean section during general anesthesia with thiopental, nitrous oxide, and halothane were studied. Forty-five minutes after tracheal extubation, a lumbar intrathecal puncture was performed, and the patients received 150 (group 1), 300 (group 2), or 450 (group 3) micrograms clonidine. Postoperative analgesia was assessed on a visual analog scale at rest and after deep cough at standard time points up to 24 h. At the same time points, blood pressure, heart rate, sedation, and respiratory rate also were recorded. RESULTS: Intrathecal clonidine decreased pain in all three groups both at rest and with coughing very shortly after injection, in a dose-dependent fashion. Clonidine 450 and 300 micrograms reduced pain scores significantly earlier (3rd and 6th min after intrathecal injection respectively), compared with 150 micrograms clonidine. Pain relief, defined as the time to first request for supplemental analgesic by patients, lasted 402 +/- 75 min in group 1, 570 +/- 76 min in group 2, and 864 +/- 80 min in group 3; significant differences among all groups; P < 0.01-0.001). Clonidine reduced mean arterial pressure compared with baseline only in group 1 (21 +/- 13%, P < 0.05). Delayed hypotension or bradycardia were not encountered after any of the three dose studies. Sedation was evident in all groups, but group 3 patients were significantly more sedated than group 1 and 2 patients. Respiratory rate and motor activity of the lower extremities were unaffected in all three groups (differences not significant). CONCLUSIONS: These results demonstrate dose-dependent analgesia after intrathecal clonidine at doses as great as 450 micrograms. The nearly immediate analgesic effect observed after intrathecal injection of 300 and 450 micrograms clonidine strongly argues for a spinal rather than a systemic site of action of this alpha 2-adrenergic agonist. After 300 and 450 micrograms intrathecal clonidine a relative hemodynamic stability is observed, suggesting a pressor effect at peripheral sites.

A dose-response study of orally administered clonidine as premedication in the elderly: evaluating hemodynamic safety.

Clonidine premedication in a dose of 5 micrograms/kg may be particularly well suited for elderly patients. To pursue this approach, sedation, intraocular pressure (IOP), and the hemodynamic profile of two doses of oral clonidine premedication were compared in 60 elderly patients, aged 65-82 yr, who underwent elective ophthalmic surgery under local anesthesia. Group 1 (n = 20) received placebo, Group 2 (n = 20) 150 micrograms of clonidine (2-2.5 micrograms/kg), and Group 3 (n = 20) 300 micrograms of clonidine (4-4.5 micrograms/kg) in a randomized, double-blind fashion. Decreases in mean arterial blood pressure were more pronounced and occurred earlier after 300 micrograms of clonidine (31.4 +/- 12.1%, P < 0.001) as compared to 150 micrograms of clonidine (18.1 +/- 10.9%, P < 0.001). Throughout the study, six patients (30%) in Group 3 (300 micrograms clonidine-treated group), but no patient in Groups 1 or 2, were treated at least once for hypotension (P < 0.05). Heart rate decreased significantly 18.5 +/- 8.1% (P < 0.001) only after 300 micrograms of clonidine. Clonidine 150 micrograms and 300 micrograms decreased IOP 32.1 +/- 14.3% (P < 0.001) and 47.8 +/- 17.2% (P < 0.001), respectively. After 150 micrograms of clonidine patients were significantly more sedated as compared to those given placebo (P < 0.01) but significantly less sedated than after 300 micrograms of clonidine (P < 0.01), where sedation persisted more than 6 h postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrathecal clonidine as a sole analgesic for pain relief after cesarean section.

In a small number of studies and isolated case reports, intrathecally administered clonidine has been reported to relieve intractable cancer pain and to prolong spinal anesthesia induced by various local anesthetics. A double-blind placebo-controlled clinical trial was carried out in order to evaluate the effect of intrathecal clonidine on pain following cesarean section. Twenty patients who underwent elective cesarean section received, 45 min after general anesthesia, either 150 micrograms (n = 10) clonidine or saline (control group, n = 10) intrathecally. Pain scores were lower in clonidine- than saline-treated patients from 20 to 120 min after intrathecal injection, as measured by a visual pain linear analog scale (P less than 0.05). Pain relief, in terms of the first supplemental analgesic request by patients, lasted 414 +/- 128 min after intrathecal clonidine and 181 +/- 169 min (mean +/- SD) (P less than 0.01) after saline. Clonidine decreased systolic, diastolic, and mean arterial pressures compared to baseline values (P less than 0.05), but heart rate and central venous pressure were unaffected (difference not significant). Maximal reduction of systolic arterial pressure was 15 +/- 9%, of diastolic arterial pressure 22 +/- 12%, and of mean arterial pressure 18 +/- 12%. Clonidine did not affect arterial hemoglobin oxygen saturation or PaCO2. Patients in the clonidine group were significantly more sedated (P less than 0.05) and more frequently reported a dry mouth (P less than 0.01) compared to the normal saline group.(ABSTRACT TRUNCATED AT 250 WORDS)