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PubMed1995

[Reflex sympathetic algodystrophies. Preventive and therapeutic aspects].

Deafferentation syndromes have in common the existence of a physical injury and/or of a functional impairment of a nerve, either somatosensory afferent (Phantom Limb Pain) and/or sympathetic efferent (Reflex Sympathetic Dystrophy). These progressively debilitating syndromes are the witness of the absence of self-limitation of neuronal sensitization, which is normally the evolution of any painful stimulation of spinal cord neurons. To some extent deafferentation syndromes could be defined as a maladaptive neuronal plasticity. The lack of complete understanding of underlying pathophysiological mechanisms gives account of the wide variety of proposed treatments and of their unpredictable and variable efficacy. This fact is also due in part to the lack of controlled studies of most of the therapeutic propositions, whose purported efficacy is usually based on anecdotal reports. Finally, the role of prevention must be strongly emphasized, focusing, if those syndromes are likely to occur following surgery, on the importance of pre- and postoperative efficient analgesia, and also, possibly, on the preemptive role of regional anaesthetic techniques.

Anesthesia, Conduction↗

PubMed2000

The clinical utility of QT interval assessment in diabetes.

A prolonged (QT) interval is considered an indicator of an increased risk of malignant ventricular arrhythmias and/or sudden death. It has been proposed that autonomic neuropathy in diabetes is related to QT interval prolongation and higher mortality rates. More recently, the interlead difference in QT interval duration has been referred to as QT interval dispersion, which has proven to be predictive of ventricular arrhythmias and mortality in different groups of patients. QT interval duration and dispersion are significantly related, but are not concordant in a substantial number of cases in identifying patients at risk. The prevalence of QT prolongation in Type 1 and Type 2 diabetic (T1 and T2DM) patients is higher than 20%. Several studies in T1 and T2DM patients have confirmed the independent relation between prolonged QT interval duration and increased QT interval dispersion and chronic ischemic heart disease. It has been consistently shown that autonomic neuropathy is related to QT interval duration, while more controversies exist on the association with QT interval dispersion. In recent years 5 studies have been published which confirm the value of QT interval as a predictor of total mortality in diabetic as well as in non-diabetic subjects. Surprisingly, no data exist on the relation between the risk of sudden death and QT interval prolongation in diabetic patients. As corrected QT interval is significantly related to mortality, it could be used to stratify the death risk in diabetic patients, particularly those who are candidates for surgery or kidney and/or pancreas transplantation. We still do not know why QT interval is prolonged and how this abnormality leads to death: however, a simple, low-cost measurement, which is easily obtainable without the need of the patient's compliance, could help select patients who need second level diagnostic procedures and strict observation.

Arrhythmias, Cardiac↗

PubMed1994

Distribution of hepatic nerve fibers in liver diseases.

Autonomic hyperactivity with increased cardiac output and other manifestations occurs in patients with both cirrhosis and noncirrhotic portal hypertension. The role of the disordered hepatic autonomic innervation in the mediation of these abnormalities is unknown. We have studied the hepatic nerve network and associated extracellular matrix proteins in patients with portal hypertension (alcoholic cirrhosis, extrahepatic portal vein obstruction, idiopathic portal hypertension), and in patients without portal hypertension (alcoholic hepatitis, psoriasis before and after treatment with methotrexate, a potentially hepatotoxic drug) by immunohistochemical methods. Histologically normal liver biopsies from patients undergoing abdominal surgery served as normal controls. Hepatic parenchymal nerves were absent in cirrhotic nodules and were depleted in the fibrotic strands of alcoholic cirrhotic livers. In alcoholic hepatitis, where clinical and histological features associated with portal hypertension were absent, nerve fibers were increased around the portal vein branches. Similar increase was also noted in liver biopsies from patients with noncirrhotic portal hypertension. Increased numbers of nerve fibers around portal veins were demonstrated in psoriatics, particularly those treated with methotrexate. Immunohistochemical studies of extracellular matrix proteins revealed apparent inverse relationships between innervation and fibronectin deposition with direct relationships to laminin staining. The association of nerve network with portal hypertension and cellular inflammation was inconsistent.

Autonomic Nervous System↗

PubMed1997

[Does decreased preoperative diagnosis in goiter surgery present special challenges for the surgeon? What stays indispensible? What is superfluous?].

Patient history, clinical examination, basal TSH, and ultrasound are the crucial factors for the indication of surgical treatment of the goiter. In our study, additional scintiscan failed to locate additional nodules found by intraoperative digital examination of the thyroid in 10.3%, and therefore leads to no additional security in determining the extent of thyroid resection (exception: autonomous goiter). Intraoperative inspection and palpation of both thyroid lobes remains the most important factor in preventing goiter recurrence.

Diagnosis, Differential↗

PubMed2006

[The heart rate variability in mice: telemetric evaluation of endotoxin shock].

BACKGROUND: Recently, the knowledge regarding all types of shock has increased. In the critical period, the maintenance of perfusion to important organs and of autonomic cardiovascular control is a clue to improve outcome. The current investigation studied the effects of endotoxin shock on the heart rate variability (HRV), which might be an early marker of multiple organ dysfunction syntion. METHODS: CL 57 BL/6 J mice (30-32 g) were implanted with intra-abdominal telemetry transmitters and data collection began 7 days after surgery and continued for 5 hours after the treatment. In endotoxin group, 3 mg x kg(-1) of E. coli lipopylysaccharide (0127 : B 8) was administered intraperitoneally and the same dose of saline was administered in control group. From the beat-by-beat values, heart rate (HR), standard deviation and coefficients of variation (RMSSD) were calculated. Integrated values of power spectral density were derived by summing depending on the frequency ranges, which were chosen with respect to the results of the previous investigation as follows: very low frequency (VLF) < 0.15 Hz; low frequency (LF), 0.15-1.5 Hz; and high frequency (HF), 1.5-5.0 Hz. RESULTS: HR showed no difference between the groups. RMSSD, Total Power, VLF, LF and HF increased in control group throughout the experiments, but, decreased in endotoxin group even 5 hr after the treatment. CONCLUSIONS: There has been scarce information on mice HRV, but we have demonstrated that endotoxin administration significantly decreases RMSSD and spectral density at low and high frequencies.

Animals↗

PubMed1996

Evaluation of the autonomic cardiovascular response in Arnold-Chiari deformities and cough syncope syndrome.

OBJECTIVE: To study the autonomic control of heart rate in patients with Arnold-Chiari deformity types I and II who exhibit the signs and symptoms of cough syncope syndrome. DESIGN: Prospective, clinical descriptive study. SETTING: University clinical research center. PATIENTS: Nine patients with Arnold-Chiari deformity and cough syncope syndrome. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Changes in heart rate, blood pressure, and electrocardiograms for power spectral analysis of heart rate variability were studied in the supine and standing positions, preoperatively (n = 9) and postoperatively (n = 5). RESULTS: Preoperatively, 8 (89%) of 9 patients increased their heart rate after postural change from supine to standing (mean +/- SD delta = 13 +/- 13 beats per minute [bpm]). Postoperatively, 4 (80%) of the 5 patients exhibited a greater increase in standing heart rate (mean delta = 19 +/- 16 bpm) compared with preoperative values. Changes in systolic, diastolic, and mean blood pressure with postural change were variable. Preoperatively, all patients exhibited abnormal control of heart rate in response to postural change. Three patients (33%) showed an abnormal decrease in low-frequency heart rate power (mean delta = -27 +/- 35 bpm2); the remaining 6 (67%) demonstrated an abnormal increase in high-frequency heart rate power (mean delta = 25 +/- 41 bpm2). All patients were clinically asymptomatic at 2 months after surgery. A normal spectral response to postural change was demonstrated in heart rate power in all 5 patients who were reevaluated postoperatively, with an increase in low-frequency power (mean delta = 33 +/- 21 bpm2) and a decrease in high-frequency power (mean delta = -21 +/- 23 bpm2). CONCLUSIONS: Patients with cervicomedullary anatomic abnormalities caused by Arnold-Chiari deformities may exhibit abnormal autonomic control of heart rate, and the autonomic control of their heart rate returns to a normal pattern after surgical palliation in conjunction with resolution of clinical symptoms.

Adolescent↗

PubMed2003

Gender and cardiac surgery.

The increased operative mortality and morbidity of women compared with men undergoing CABG surgery results from multiple differences in presentation, preoperative risk profile, and surgical factors. Investigators have found consistently that women present with a different preoperative risk profile than do men. Women more commonly have factors associated with increased short- and long-term mortality, such as less frequent use of IMA grafts. Differences in study design and patient population may contribute to variability in short- and long-term mortality among the various studies. The lack of representation of women in older clinical trials has hindered our understanding of the management of CAD in women; this situation must be remedied in future studies, [95]. Known physiologic and anatomic differences must be evaluated for their effects on outcomes. Further studies are needed to evaluate gender-related differences in autonomic responses to acute coronary occlusion, complications related to cardiopulmonary bypass, susceptibility to abnormalities in coagulation, and other factors that might account for discrepant outcomes in men versus women undergoing CABG [96]. Beyond these factors, specific pharmacologic and therapeutic considerations, such as the role of estrogen replacement therapy, need to be clarified. As further knowledge accumulates, it is hoped that gender-specific risk factors can be mitigated and protective factors exploited, thereby improving the outcomes for all cardiac surgery patients.

Cardiac Surgical Procedures↗

PubMed2003

The effect of intraoperative use of esmolol and nicardipine on recovery after ambulatory surgery.

UNLABELLED: There is controversy regarding the optimal technique for maintaining hemodynamic stability during anesthesia. We designed this prospective, randomized, double-blinded study to test the hypothesis that the technique used for maintaining hemodynamic stability during general anesthesia can influence recovery after ambulatory surgery. Forty-five healthy consenting women undergoing gynecologic laparoscopy procedures were randomly assigned to 1 of 3 treatment groups: Group 1 (control, n = 15) received normal saline 5 mL and 1 mL, followed by a saline infusion at a rate of 0.005 mL x kg(-1) x min(-1); Group 2 (n = 15) received esmolol 50 mg and saline 1 mL, followed by an esmolol infusion 5 microg x kg(-1) x min(-1); and Group 3 (n = 15) received esmolol 50 mg and nicardipine 1 mg, followed by an esmolol infusion 5 microg x kg(-1) x min(-1). The study drugs were administered after the induction of anesthesia with fentanyl 1.5 microg/kg, and propofol 2 mg/kg I.V. Tracheal intubation was facilitated with vecuronium 0.12 mg/kg I.V. Anesthesia was initially maintained with desflurane 2% end-tidal and N(2)O 67% in oxygen in all 3 groups. During surgery, the mean arterial blood pressure (MAP) was maintained within +/-15% of the baseline value by varying the study drug infusion rate and the inspired concentration of desflurane. In addition to MAP and heart rate values, electroencephalogram bispectral index values were recorded throughout the perioperative period. Recovery times and postoperative side effects were assessed. Compared with the control group, adjunctive use of esmolol and nicardipine attenuated the increase in heart rate (in Group 2) and MAP (in Group 3) after tracheal intubation. Furthermore, the use of an esmolol infusion as an adjunct to desflurane to control the acute autonomic responses during the maintenance period significantly decreased emergence times (4 +/- 2 versus 7 +/- 4 min), decreased the need for postoperative opioid analgesics (43% versus 80%), and reduced the time to discharge (209 +/- 89 versus 269 +/- 100 min). We conclude that the adjunctive use of esmolol alone or in combination with nicardipine during the induction of anesthesia reduced the hemodynamic response to tracheal intubation. Furthermore, use of an esmolol infusion as an adjuvant to desflurane-N(2)O anesthesia for controlling the acute hemodynamic responses during the maintenance period improved the recovery profile after outpatient laparoscopic surgery. IMPLICATIONS: The adjunctive use of the beta-adrenergic blocker esmolol to control the acute sympathetic responses during desflurane-based anesthesia provided a more rapid awakening from anesthesia, reduced the postoperative opioid analgesic requirement, and decreased the time to discharge home after ambulatory laparoscopic surgery.

Adrenergic beta-Antagonists↗

PubMed2005

Low to high frequency ratio of heart rate variability spectra fails to describe sympatho-vagal balance in cardiac patients.

Heart rate variability (HRV) reflects an influence of autonomic nervous system on heart work. In healthy subjects, ratio between low and high frequency components (LF/HF ratio) of HRV spectra represents a measure of sympatho-vagal balance. The ratio was defined by the authorities as an useful clinical tool, but it seems that it fails to summarise sympatho-vagal balance in a clinical setting. Value of the method was re-evaluated in several categories of cardiac patients. HRV was analysed from 24-hour Holter ECGs in 132 healthy subjects, and 2159 cardiac patients dichotomised by gender, median of age, diagnosis of myocardial infarction or coronary artery surgery, left ventricular systolic function and divided by overall HRV into several categories. In healthy subjects, LF/HF ratio correlated with overall HRV negatively, as expected. The paradoxical finding was obtained in cardiac patients; the lower the overall HRV and the time-domain indices of vagal modulation activity were the lower the LF/HF ratio was. If used as a measure of sympatho-vagal balance, long-term recordings of LF/HF ratio contradict to clinical finding and time-domain HRV indices in cardiac patients. The ratio cannot therefore be used as a reliable marker of autonomic activity in a clinical setting.

Autonomic Nervous System↗

PubMed1990

Thyroid carcinoma mimicking a toxic adenoma.

A young woman with a thyroid papillary carcinoma behaving as an autonomously hyperfunctioning nodule is described. Only 17 similar patients have been seen in the past 25 years. It is emphasized that hyperthyroidism does not exclude malignant disease in hot nodules. This possibility suggests that all thyroid nodules, either cold or hot, require careful management. Therefore, in "at risk" cases, surgery could be the most useful treatment.

Adenoma↗

PubMed1994

[The effect of thoracic epidural anesthesia on the pathophysiology of the eventration syndrome].

Abdominal mesenteric traction (MT) results in decreased mean arterial pressure (MAP), systemic vascular resistance (SVR) and increased cardiac output (CO). This response is induced by a considerable release of prostacyclin (PGI2). Precipitous falls in systemic arterial pressure related to central and/or autonomic nervous reflex arcs also have been described during operations on the upper abdominal viscera. Those hypotensive responses to visceral traction appear to be transmitted along afferent fibres contained within the splanchnic nerves. We investigated the influence of supplementary thoracic epidural anaesthesia on mesenteric traction response during major abdominal surgery. METHODS. With the approval of the Human Investigation Review Board we studied 40 patients scheduled for major abdominal surgery (infrarenal aortic, gastrointestinal and pancreatic surgery) according to a prospective, randomized double-blinded protocol. Patients were randomized to two different anaesthetic regimens. Patients in group 1 received general anaesthesia (GA n = 20) with 0.1-0.15 mg/kg midazolam and 10 micrograms/kg fentanyl prior to skin incision. Maintenance included 65% nitric oxide in oxygen and 0.1 mg increments of fentanyl as required. Group 2 patients (EA n = 20) underwent a combined technique of dose-reduced general anaesthesia and supplementary continuous, thoracic epidural anaesthesia (bupivacaine 0.25%, sensory blockade T4 to L1-3). In both anaesthesia groups ibuprofen (400 mg i.v.) or a placebo equivalent was administered 15 min before the induction of anaesthesia. MT was applied in a uniform fashion. Baseline values preceded the incision of the peritoneum. Further assessments followed 5, 15 and 30 min after MT. The plasma concentrations of 6-keto-PGF1 alpha (stable metabolite of PGI2), TXB2 (stable metabolite of thromboxane), PGF2 alpha, KH2-PGF2 alpha (stable metabolite of PGF2 alpha) were determined by radioimmunoassay. At all assessments we recorded systolic and diastolic blood pressure, heart rate and measured arterial blood gases. Statistical analyses were performed using three-factor ANOVA for repeated measurements after log(x) transformation. A P-value of less than 0.05 was considered significant when the Bonferroni-Holm adjustment was applied. RESULTS. Patients with supplementary epidural anaesthesia demonstrated lower systolic (P = 0.0001) and diastolic (P = 0.006) blood pressure than those in the GA group. Nevertheless, in untreated patients in the EA and GA group there was a significant decrease of about 20-30% in systolic and diastolic blood pressure (P = 0.0001) after mesenteric traction. Irrespective of the anaesthetic procedure, paO2 (P = 0.0001) decreased after mesenteric traction in the placebo group. The control patients in the GA group exhibited a more pronounced increase in heart rate after MT. After traction on the mesentery a significant 20- to 30-fold increase in 6-keto-PGF1 alpha plasma concentrations occurred in the placebo group: GA group 1950/58 (5 min), 1574/59 (15 min) 858/66 (30 min) ng/l, P < 0.0001; EA group: 2002/106 (5 min), 2955/107 (15 min) 1807/70 (30 min) ng/l, P < 0.0001, for placebo vs ibuprofen. There was no statistically significant difference between the two anaesthetic procedures used. In ibuprofen-pretreated patients haemodynamics and paO2 values were stable, while 6-keto-PGF1 alpha plasma concentrations remained within the normal range. CONCLUSION. Our data clearly indicate that the mesenteric traction response consists in relevant haemodynamic alterations and a significant decrease of paO2. Stable haemodynamics and paO2 following cyclooxygenase inhibition signify an action mediated by prostacyclin. Deafferentation of the splanchnic nerves by supplementary thoracic epidural anaesthesia did not influence either prostacyclin release or the decrease in blood pressure and paO2 after traction on the mesentery root...

Abdomen↗

PubMed2000

Ethical issues in parental decision-making. An interview study of mothers of children with hypoplastic left heart syndrome.

It is unclear how parents make life-and-death decisions on behalf of their children. To address this issue we interviewed 20 mothers whose children were born with hypoplastic left heart syndrome (HLHS), 10 whose child survived the operations and 10 mothers who chose comfort care. Semistructured interviews lasting from 1.5 to 3.5 h took place on median 4.6 (range 2.5-6) years after birth. The mothers who chose comfort care had more years of education (p = 0.03), reported a better childhood environment (p = 0.05) and had more often been employed in the healthcare services. The two groups described the information received in similar terms. The main motive for choosing surgery was that this was perceived to be the only acceptable choice. The motive for choosing non-treatment was to prevent the child from suffering. Lack of knowledge about long-term outcome, a state of shock and short time to deliberate limit the parents' possibilities for making autonomous choices. Autonomous decisions may be neither possible nor desirable for all parents. The care perspective, which highlights the parents' preferences resources and values, should represent ethical guidelines for care providers willing to dicide on behalf of the child.

Adult↗

PubMed1987

Corticotropin-releasing factor acts on the brain to reduce gastric contractility.

Various stressors (cold restraint, electric shock, etc.) applied to rats increase gastric contractility and are associated with gastric erosions. Intracisternal (i.c.) thyrotropin-releasing hormone (TRH) increases contractility, gastric acid secretion and the incidence of erosion formation. Corticotropin-releasing hormone (CRF) is released by stress, and acting centrally produces autonomic and endocrine changes. We have studied the role of i.c. CRF on gastric contractility in anesthetized rats (n = 6). Contractility was measured by extraluminal force transducers sutured to the gastric corpus. Frequency, amplitude of contractions and a motility index were analyzed by computer. Baseline measures, after recovery from surgery were obtained in 24-hour fasted rats. Contractility was stimulated by intravenous carbachol (100 mg/kg/h) or i.c. injection of the TRH analog, RX 77368. Contractility thus induced was inhibited by intravenous atropine (1 mg/kg). CRF (30-1,000 ng i.c.) produced a dose-dependent suppression of RX 77368 (p less than 0.05) but had no effect on that induced by intravenous carbachol; saline i.c. had none either. Intravenous CRF was 1/10th as potent in suppressing contractions produced by i.c. RX 77368. Diminution of gastric contractions after i.c. CRF (1 mg) occurred within 5 min of administration, and lasted for at least 60 min. These data show that i.c. CRF injection acts centrally to inhibit gastric contractions stimulated centrally (i.e. by i.c. RX 77368) but not peripherally (i.e. by carbachol), and by inference reduces the risk of erosion formation induced by some stressors.

Animals↗

PubMed1978

Left stellectomy in the long QT syndrome.

Recent investigations have reaffirmed the role of autonomic innervation of the heart in the genesis of certain cardiac arrhythmias. The long QT syndrome (LQTS) has been described for years, but only recently has evidence of its link to autonomic imbalance been established. A case of LQTS is presented with intraoperative evidence at the time of left stellectomy of life-threatening arrhythmias triggered by stimulation of this neural body. Removal of the left stellate ganglion normalized the electrocardiographic (ECG) abnormalities and has rendered the patient asymptomatic since surgery. Left stellectomy may become definitive therapy for selected patients with the LQTS.

Adult↗

PubMed1991

Exercise training after cardiac transplantation.

During the last decade, cardiac transplantation has become the accepted form of treatment for selected patients with end-stage heart disease, which usually results from dilated cardiomyopathy or coronary artery disease. Although 5-yr survival is currently 85%, patients have complicated courses after surgery, with an ever present risk of infection and graft rejection. Because of physical inactivity and severe limitation of cardiac output preoperatively, these deconditioned patients are excellent candidates for medically supervised rehabilitative exercise training programs. Denervation of the myocardium, which occurs with cardiac transplantation, results in a loss of autonomic nervous system modulation of cardiac output, with reliance on circulating catecholamines and with a delayed heart rate and cardiac output response to the onset of exercise. Oxygen uptake kinetics are prolonged, and maximal oxygen uptake is reduced. Additional abnormalities in cardiac and pulmonary artery pressures and in ventilation during exercise have been described. The literature contains seven studies concerning the effects of exercise training in cardiac transplant recipients. Benefits resulting from training include increases in maximal oxygen uptake, peak exercise power output, anaerobic threshold, and lean body mass, reduced perceived exertion, heart rate, and blood pressure during submaximal exercise, and a lowered resting heart rate and blood pressure. There are no data to suggest that exercise training alters the incidence of infection or rejection or improves longevity or return to pre-illness lifestyle.

Coronary Disease↗

PubMed2005

Surgical salvage of recurrent rectal cancer after transanal excision.

PURPOSE: This study examines surgical salvage of locally recurrent rectal cancer following transanal excision of early tumors. METHODS: Through retrospective review of a colorectal database we identified 50 patients who underwent attempted surgical salvage for local recurrence following initial transanal excision of T1 or T2 rectal cancer. Eight patients had resectable synchronous distant disease. Clinicopathologic variables were associated with extent of surgery required for salvage and outcome. RESULTS: Salvage procedures included abdominoperineal resection (31), low anterior resection (11), total pelvic exenteration (4), and transanal excision (3). One patient had unresectable disease at exploration, requiring diverting ostomy. Of the 49 patients who underwent successful salvage, 27 (55 percent) required an extended pelvic dissection with en bloc resection of one or more of the following structures: pelvic sidewall and autonomic nerves (18); coccyx or portion of sacrum (6); prostate (5); seminal vesicle (5); bladder (4); portion of the vagina (3); ureter (2); ovary (1); and uterus (1). Complete pathologic resection (R0) was accomplished in 47 of 49 patients. Of the eight patients with distant and local recurrence, two underwent synchronous resection and six had delayed metastasectomy. With a median follow-up of 33 months, 29 patients had recurred or died of disease at the time of this analysis. Five-year disease-specific survival was 53 percent. Factors predictive of survival included evidence of any mucosal recurrence on endoscopy, low presalvage carcinoembryonic antigen, and absence of poor pathologic features (lymphovascular and perineural invasion). Patients who required an extended pelvic resection had a worse survival rate. CONCLUSION: Pelvic recurrence following transanal excision of early rectal cancer is often locally advanced, requiring an extended pelvic dissection with en bloc resection of adjacent pelvic organs to achieve salvage. The long-term outcome in patients undergoing resection is less than expected, considering the early stage of their initial disease. When contemplating local excision for early rectal cancer, the risk of local recurrence, the extent and morbidity of surgery required for salvage, and the modest cure rate following salvage should be considered.

Adult↗

PubMed1975

Radiology in chemical sympathectomy.

Chemical sympathectomy is an alternative to surgical sympathectomy when the patient's age or general condition precludes surgery. The indications and rationale in lower-limb arterial disease are discussed, and it is suggested that X-ray control is a valuable adjunct to the procedure.

Ganglia, Autonomic↗

PubMed1987

Severe cardiovascular changes associated with pancuronium after cardiopulmonary resuscitation and after brain injury.

Severe hypertension, tachycardia or ECG changes have been reported following i.v. administration of pancuronium to patients with pheochromocytoma or bronchial asthma. These cardiovascular changes were explained by an interaction between autonomic effects of pancuronium and elevated serum catecholamines or aminophylline. We noted similar cardiovascular changes associated with i.v. administration of pancuronium in two patients after successful cardiopulmonary resuscitation and in two with midbrain hemorrhage and epidural hematoma. In these patients, pancuronium produced no abnormal cardiovascular changes when given during elective surgery or before the occurrence of midbrain hemorrhage. Thus, ischemic brain damage may play a role in producing the severe cardiovascular changes associated with pancuronium.

Aged↗