Gastrointestinal symptoms in HIV-positive kidney transplant candidates and recipients from an HIV-positive donor.

Gastrointestinal symptoms (GIS) are common in kidney transplant candidates and recipients and may be worsened by HIV. Objective: To determine the frequency and severity of GIS in HIV-positive kidney transplant recipients from HIV-positive donors, and those waiting to receive one. A GIS rating scale (GSRS) was completed by 76 participants at baseline and at 6 months. GIS frequency was defined as having at least one symptom (GSRS > 1). Severity was indicated by the GSRS score. Transplant candidates: GIS frequency was 88.9% and 86.3% at baseline and 6 months respectively. Indigestion was the most frequent (79.6% and 66.7% at baseline and 6 months), and severe GIS (GSRS 2.3). Women reported global mean (p = 0.030) severity significantly more than men. Transplant recipients: GIS frequency was 95.2% and 76.2% at baseline and 6 months respectively. At both assessment points, indigestion occurred most frequently (85.7% and 61.9% respectively). Highest GSRS was reported for indigestion at baseline (2.33) and at 6 months (1.33). Waist circumference (WC) was positively associated with the severity of constipation GSRS. GIS are common in both groups, especially indigestions. WC in transplant recipients should be monitored.

Omapatrilat limits infarct size and lowers the threshold for induction of myocardial preconditioning through a bradykinin receptor-mediated mechanism.

Bradykinin is an important endogenous trigger of myocardial ischemic preconditioning (IPC). Through simultaneous inhibition of neutral endopeptidase and angiotensin converting enzyme, omapatrilat prevents enzymatic degradation of bradykinin. The aim of this study was to investigate if omapatrilat, through its ability to augment bradykinin levels, can augment a subthreshold IPC stimulus (Sub-IPC) and to compare the action of omapatrilat with the angiotensin-converting enzyme inhibitor, captopril. Langendorff perfused rat hearts were subjected to 35 min left coronary artery occlusion and 120 min reperfusion. Full IPC was induced with 5 min global ischemia/10 min reperfusion and substantially limited infarct size (21.5 +/- 3.5% of risk zone vs 53.4 +/- 2.0% in controls, P < 0.01). Sub-IPC (2 min global ischemia/10 min reperfusion) did not limit infarct size (48.4 +/- 3.8%). Omapatrilat (10 micromol/L) or captopril (200 micromol/L) were administered alone or in conjunction with Sub-IPC. Reduced infarct size comparable to that observed with the full IPC protocol was seen when sub-IPC was combined with either omapatrilat (19.7 +/- 2.5%) or captopril (20.3 +/- 4.9%). Omapatrilat alone caused modest reduction of infarct size (34.6 +/- 1.5%, P < 0.01 v control), an effect not observed with captopril. Hoe140, a selective kinin B(2) receptor antagonist, eliminated the cardioprotective effect of omaptrilat alone or in combination with sub-IPC. We conclude that omapatrilat elicits cardioprotection via inhibition of bradykinin degradation and that dual inhibition of angiotensin-converting enzyme and neutral endopeptidase may have beneficial effects beyond standard angiotensin-converting enzyme inhibitor therapy in patients with acute coronary syndromes who are at risk of myocardial infarction.

Bradykinin elicits "second window" myocardial protection in rat heart through an NO-dependent mechanism.

Bradykinin is an important endogenous mediator exerting acute protective effects in the ischemic myocardium. The aims of this study were to investigate whether exogenously administered bradykinin could evoke delayed myocardial protection and to determine whether any protection observed might be dependent on nitric oxide (NO) generation. Conscious rats received bradykinin (40 microg/kg iv) or saline, preceded 15-20 min earlier by the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg ip) or saline. Twenty-four hours later, hearts were Langendorff perfused and subjected to 35 min of regional ischemia and 120 min of reperfusion. Infarct size was assessed using tetrazolium staining and expressed as a percentage of the risk zone. Bradykinin pretreatment reduced the infarct-to-risk ratio from 53.5 +/- 3.2% to 29.1 +/- 4.7% (P < 0.01). The administration of L-NAME before bradykinin abrogated the delayed protection (infarct size 52.3 +/- 5.0%) but alone did not influence infarct size (53.5 +/- 4.8%). These results are the first to demonstrate that bradykinin can evoke a delayed ("second window") enhancement of myocardial tolerance to ischemia, an action that is dependent on the early generation of NO.

The influence of scalp infiltration with bupivacaine on hemodynamics and postoperative pain in adult patients undergoing craniotomy.

UNLABELLED: After craniotomy, hypertension may contribute to intracerebral hemorrhage. We studied whether scalp infiltration with bupivacaine during craniotomy reduces postoperative pain and hypertension. In a double-blind fashion, 36 adult patients (ASA physical status II or III) undergoing elective craniotomy were randomly assigned to receive scalp infiltration with either bupivacaine (0.25%) and epinephrine (1:200,000) or saline/ epinephrine (1:200,000) for skeletal fixation, skin incision, and wound closure. Heart rate (HR) and mean arterial pressure (MAP) were measured after anesthesia induction, after skull-pin insertion, after scalp infiltration, during dural closure, during skin closure, on admission to postanesthesia care unit (PACU), and 1 h after admission. Visual analog pain scores were recorded in the PACU. MAP was significantly greater in the saline group at scalp infiltration. HR was significantly faster in the saline group at dural and skin closure. The bupivacaine group reported significantly less pain than the saline group at PACU admission and 1 h after admission. Pain scores did not correlate with hemodynamic measurements. We conclude that scalp infiltration with 0.25% bupivacaine with 1:200,000 epinephrine blunts certain intraoperative hemodynamic responses and reduces postoperative pain but has no effect on postoperative hemodynamics. IMPLICATIONS: We sought to evaluate whether scalp infiltration with bupivacaine and epinephrine at the beginning and end of craniotomy would afford more intra- and postoperative hemodynamic stability and influence immediate postoperative pain. We found that intraoperative hemodynamics were not influenced greatly; however, craniotomy patients do have significant postoperative pain, which does not seem to have an influence on hemodynamics in the postanesthesia care unit.

Effect of cranial surgery and brain tumor size on emergence from anesthesia.

BACKGROUND: Knowing which neurosurgical patients are at risk for delayed awakening may lead to better utilization of intensive care resources and avoid the risk and cost of pharmacologic reversal and diagnostic tests. METHODS: The authors compared anesthetic emergence from complex spinal surgery (spine; n = 47) with that from craniotomy for supratentorial nonfrontal (n = 22), frontal (n = 34), or posterior fossa tumor (n = 28). A further comparison involved patients with small versus large (diameter > 30 mm, mass effect) tumors. The standardized anesthetic regimen consisted of induction with 2-4 mg/kg-1 thiopental and 1-2 micrograms/kg-1 sufentanil, followed by maintenance with nitrous oxide, 0.2-0.5 micrograms.kg-1.h-1 sufentanil and < or = 0.5% isoflurane. Sufentanil administration was terminated on dural or spinal muscle closure, isoflurane during skin closure, and nitrous oxide during dressing application. After discontinuing nitrous oxide, a minineurologic examination was performed every 15 min for 1 h, then hourly for 4 h and at 24 h. RESULTS: Craniotomy patients performed less well than spinal surgery patients on the minineurologic examination 15 and 30 min after discontinuing nitrous oxide. At 15 min, fewer patients with large (vs. small) tumors were oriented to time (58% vs. 87%; P < 0.01) or place (67% vs. 90%; P < 0.01). Forty-two percent of patients with large tumors still had an abnormal minineurologic examination score versus 15% of patients with small tumors. At 30 min, these values were 28% and 8%, respectively (P < 0.05). Seventy-one percent of patients with large tumors were oriented to time compared to 97% for small lesions (P < 0.01). Emergence from anesthesia was similar for spinal surgery patients and patients with small brain tumors. CONCLUSION: Patients undergoing craniotomy for large intracranial mass lesions awaken more slowly than patients after spinal surgery or craniotomy for small brain tumor.

Analysis of catecholamine and vasoactive peptide release in intracranial arterial venous malformations.

Craniotomy for resection of cerebral arterial venous malformation has been associated with postoperative hypertension, which necessitates administration of large doses of antihypertensive medications to control blood pressure. Controlling blood pressure is essential because hypertensive episodes can lead to postoperative cerebral hemorrhage with increases in morbidity and mortality. We measured vasoactive peptide and catecholamine release in 13 patients who underwent resection of an arterial venous malformation and in a control group of 6 patients who presented for clipping of unruptured cerebral aneurysms. Plasma renin activity, angiotensin I and II, vasopressin, aldosterone, epinephrine, and norepinephrine levels were measured intraoperatively and for 36 h postoperatively. Analysis of variance was used to assess sample and group effects. A significant interaction between sample and groups was found for norepinephrine (p < 0.001) and renin (p = 0.002). Our data suggest that elevated plasma renin and norepinephrine levels are in part responsible for postoperative hypertension in patients undergoing resection of arterial venous malformations. Blocking the release of these hormones may help control blood pressure after surgery for removal of arterial venous malformations.

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy.

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3-10 years, were randomized to receive 10, 20, or 30 micrograms.kg-1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively, vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose was significantly lower in Group C (38.6 +/- 47 micrograms versus 79.1 +/- 74 and 189.6 +/- 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 micrograms.kg-1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 micrograms.kg-1 dose.

Pharmacokinetic origin of carbamazepine-induced resistance to vecuronium neuromuscular blockade in anesthetized patients.

BACKGROUND: Patients receiving chronic carbamazepine therapy have shortened recovery times from a neuromuscular block induced by vecuronium. The current study investigates the pharmacokinetic or pharmacodynamic mechanisms responsible for this observation. METHODS: Pharmacokinetics and pharmacodynamics of 0.1 mg/kg intravenous bolus vecuronium in ten epileptic patients receiving chronic carbamazepine therapy were compared to that of ten control subjects. All patients were scheduled for neurosurgery while anesthetized with isoflurane and sufentanil. Arterial blood samples were collected for 6 h. Plasma vecuronium concentrations were measured by high-performance liquid chromatography coupled to electrochemical detection. The adductor pollicis force of contraction was recorded after supramaximal ulnar nerve stimulation. Plasma vecuronium concentrations were fitted to a two-compartment pharmacokinetic model, and the effect compartment equilibration rate constant was derived with a nonparametric link model. The effect compartment concentrations were fitted to a sigmoid Emax model. Results were compared using Student's t-test for independent samples. RESULTS: In the carbamazepine group, the mean recovery times to T(1) 25% were shorter (28.1 +/- 3.4 vs. 47.3 +/- 5.1 min in control subjects; P=0.007), and the T(1) 25% to T(1) 75% recovery index was decreased (7.6 +/- 1.2 vs. 21.9 +/- 6.8 min in control subjects; P=0.025). No changes in onset times were observed. Clearance was 9.0 +/- 1.2 ml x kg-1 x min-1 versus 3.8 +/- 0.3 in the control group (P=0.003), whereas no changes in volumes of distribution at steady-state were observed. Therefore, the mean residence time was halved (17.8 +/- 2.5 vs. 31.9 +/- 2.5 min in control subjects; P=0.001). No differences in the effect compartment equilibration rate constant, vecuronium effect compartment concentration present at a 50% block (EC50), or slope of the sigmoid between the two groups were found. CONCLUSIONS: The twofold increase in clearance provides evidence of a pharmacokinetic origin to the carbamazepine-vecuronium interaction; however, the possibility of a concurrent pharmacodynamic alteration cannot be assessed. Greater knowledge of protein drug binding needs to be acquired to give a meaningful interpretation to the similar EC50 values observed in the two groups.

The effect of propofol on the electroencephalogram of patients with epilepsy.

The effect of propofol on the electroencephalogram (EEG) in patients with epilepsy is still unclear. Case reports with electroencephalographic documentation highlight pro- and anticonvulsant effects and beta activation of the EEG. This prospective study sought to determine the effect of propofol in 17 patients undergoing cortical resection for intractable epilepsy. Each patient received 2 mg/kg of propofol intravenously and the EEG was recorded from chronically implanted subdural electrodes placed during a previous craniotomy. Frequency of interictal spikes, time to burst suppression, and appearance of beta activation were recorded. The median frequency of interictal spikes decreased significantly from 2 spikes/min before to 0 spikes/min after propofol (P = 0.001). Seizure activity did not increase after propofol. Profound burst suppression and an increase in beta activity were noted consistently. The use of propofol in patients with epilepsy seems to be safe but may interfere with the recording of EEG spikes.

Influence of carbamazepine on the dose-response relationship of vecuronium.

We have determined the cumulative dose-response relationship for vecuronium from the evoked compound electromyogram of the hypothenar muscles in eight patients who were receiving carbamazepine. The ED50, ED90 and ED95 were 29, 52 and 64 micrograms kg-1, respectively, and were significantly different (P < 0.05) from those of a control group (ED50, ED90 and ED95 21, 36 and 44 micrograms kg-1, respectively).

Monoamine oxidase inhibitors and elective surgery.

Monoamine oxidase inhibitor use is considered a contraindication for elective surgery. We reviewed 32 patients on a regimen of isocarboxazid 10 mg daily who underwent elective surgery. Their anesthetic management, postanesthesia outcome, and pharmacology are described.

Intravenous sedation for MR imaging of the brain and spine in children: pentobarbital versus propofol.

The authors present a prospective study of single-agent pediatric sedation regimens for patients older than 2 years of age undergoing magnetic resonance (MR) imaging of the brain and spine. Thirty patients underwent MR imaging after intravenous administration of pentobarbital in successive boluses of 2.5 mg/kg to a maximum of 7.5 mg/kg. Thirty-one patients received an intravenous bolus followed by continuous infusion of propofol. The dosage schedule for propofol was 2 mg/kg (with supplemental 1 mg/kg boluses) followed by continuous infusion of 6 mg/kg per hour. There was no significant difference in the physiologic response to sedation between the two groups, although the magnitude of the drop in pulse was significantly greater in the group receiving propofol. Three patients receiving propofol experienced transient decreases in oxygen saturation, at variable times over the course of the procedure. However, patients recovered significantly faster from sedation with propofol. While propofol may represent a viable alternative to pentobarbital in selected patients, propofol requires constant physician supervision and meticulous technique.

Vascular pressures and cortical blood flow in cavernous angioma of the brain.

This study was designed to investigate the hemodynamic characteristics of cavernous angiomas of the brain. Five adult patients with a cavernous angioma underwent local cortical blood flow studies and vascular pressure measurements during surgery for the excision of the cavernous angioma. Clinical presentation included headache in four patients, seizures in four patients, and recurring diplopia in one patient. Magnetic resonance imaging demonstrated the cavernous angiomas in all patients and revealed an associated small hematoma in two. Four patients with a cerebral cavernous angioma were operated on in the supine position and the remaining patient, whose lesion involved the brain stem, was operated on in the sitting position. Mean local cortical blood flow (+/- standard error of the mean) in the cerebral cortex adjacent to the lesion was 60.5 +/- 8.3 ml/100 gm/min at a mean PaCO2 of 35.0 +/- 0.6 torr. Mean CO2 reactivity was 1.1 +/- 0.2 ml/100 gm/min/torr. The local cortical blood flow results were similar to established normal control findings. Mean pressure within the lesion in the patients undergoing surgery while supine was 38.2 +/- 0.5 mm Hg; a slight decline in cavernous angioma pressure occurred with a drop in mean systemic arterial blood pressure and PaCO2. Mean pressure in the cavernous angioma in the patient operated on in the sitting position was 7 mm Hg. Jugular compression resulted in a 9-mm Hg rise in cavernous angioma pressure in one supine patient but no change in the patient in the sitting position. Direct microscopic observation revealed slow circulation within the lesions. The hemodynamic features demonstrated in this study indicate that cavernous angiomas are relatively passive vascular anomalies that are unlikely to produce ischemia in adjacent brain. Frank hemorrhage would be expected to be self-limiting because of relatively low driving pressures.

Local cortical blood flow and oxygen consumption during isoflurane-induced hypotension. Results in patients undergoing intracranial aneurysm clipping.

Cerebral cortical blood flow (lCoBF) and metabolic rate for oxygen (lCoMRO2) were studied in eight patients undergoing intracranial aneurysm clipping. The patients were anesthetized with fentanyl 10 micrograms/kg and 70% nitrous oxide combined with 30% oxygen. Hypotension was induced with isoflurane. A thermal diffusion probe was used to measure lCoBF, and arterial and cerebral venous blood samples were obtained for measurement of arterio-cerebral venous O2 content difference. Measurements were made prior to hypotension, during hypotension (to mean arterial pressure approximately 50 mmHg), and posthypotension. Mean lCoBF decreased from 69 +/- 20 mL/100 g/min at normotension to 59 +/- 13 mL/100 g/min during hypotension (P less than .03, NS) and was 61 +/- 18 mL/100 g/min upon return to normotension (all values mean +/- 1 SD). The lCoMRO2 averaged 3.9 +/- 1.6 mL/100 g/min and 3.1 +/- 1.5 mL/100 g/min, respectively (P less than .03, NS) for normotension upsilon hypotension. Values for cerebral venous PO2 and O2 saturation also did not differ significantly between study periods. These results indicate that isoflurane-induced hypotension during fentanyl-nitrous oxide anesthesia allows maintenance of a constant lCoBF and oxygen delivery.

Altered cerebral autoregulation and CO2 reactivity after aneurysmal subarachnoid hemorrhage.

Disruption of local cortical blood flow (CBF) autoregulation and CO2 reactivity, or vasoparalysis, has been documented in humans after aneurysmal subarachnoid hemorrhage (SAH). Generally, the degree of vasoparalysis is related to the patient's clinical grade. Using intraoperative measurement of local CBF, we evaluated pressure autoregulation and CO2 reactivity in patients after SAH. Fourteen patients with SAH and 10 patients with asymptomatic aneurysm underwent craniotomy for clipping of their aneurysms. During operation, local CBF was recorded with thermal conductivity probes placed on the middle frontal gyrus, 4 to 6 cm from the nearest point of retraction. Before retractor placement, CBF was measured with the PCO2 at 25 and 35 mm Hg and the mean arterial blood pressure (MABP) between 70 and 80 mm Hg. After aneurysm clipping, flows were again measured. With the PCO2 at 25 mm Hg, the MABP was raised from 65 to 85 mm Hg. The PCO2 was then allowed to rise to 35 mm Hg, after which the MABP was lowered from 85 to 65 mm Hg. Six patients underwent operation within the 1st week after SAH (Grade I, n = 3; Grade II, n = 3). The remainder (n = 8) were operated on 9 days to 3 months after SAH. After aneurysm clipping, significant CBF changes (P less than 0.001) with PCO2 alteration occurred in control patients and those operated on more than 7 days after SAH. There was no significant change in CBF in patients operated on within 7 days after SAH. Changes in CBF reactivity to alteration of MABP were significantly larger in early operation patients than in other groups (P less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral circulation during arteriovenous malformation operation.

The circulatory changes in the cortex around a cerebral arteriovenous malformation (AVM) were studied in 18 patients. The AVMs had rapid circulation times with early draining veins on angiography. Local cortical blood flow (lCoBF) was measured with cortically applied thermister/Peltier stack arrays. The AVMs had a more pronounced effect on lCoBF at a 2- to 4-cm distance from the AVM margin than in the adjacent cortex. Mean preexcision lCoBF was 62.9 +/- 6.7 (SE) ml/100 g/minute (i.e., similar to normal controls) near the AVM margin and 43.0 +/- 4.2 ml/100 g/minute far (i.e., greater than 2 cm) from the AVM. CO2 reactivity (COR) before excision was 1.1 +/- 0.3 ml/100 g/minute/torr of CO2 (i.e., similar to normal controls) at near sites and 0.6 +/- 0.3 ml/100 g/minute/torr of CO2 at far sites. The mean postexcision near lCoBF remained stable at 55.8 +/- 5.1 ml/100 g/minute at near sites, but the far lCoBF significantly increased (P less than 0.05) to 57.2 +/- 6.8 ml/100 g/minute. The cortical feeding artery pressure was substantially below the normal cortical artery pressure in 50% of the cases studied. Pressure in these arteries normalized after occlusion and AVM excision, resulting in a rapid increase in cortical artery perfusion pressure. Draining red vein pressure, which was elevated before AVM excision, also dropped after excision, contributing to the increase in perfusion pressure. Two patients who developed the normal perfusion pressure breakthrough syndrome (PBS) after operation had low lCoBF and disturbed COR before AVM excision and marked increase of lCoBF after excision.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of etomidate on the electroencephalogram of patients with epilepsy.

Etomidate was given intravenously to 12 epileptic patients undergoing craniotomy for surgical removal of their seizure focus. Electroencephalograms were recorded by means of subdural electrodes. Nine of the 12 patients showed an increase in epileptiform activity. In six of the nine patients, the activity was marked.