Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction.

BACKGROUND: Adenosine is analgesic in humans, and the selective adenosine A1 receptor agonist GR79236X has significant anti-nociceptive activity in an animal pain model of inflammatory pain. METHODS: Seventy-nine patients with moderate pain after third molar extraction under general anaesthesia were randomized to receive a 15 min double-blind infusion containing either GR79236X 4 microg kg-1, GR79236X 10 microg kg-1, diclofenac 50 mg, or saline placebo. Rescue analgesia was promptly available to all patients. RESULTS: Meaningful pain relief (mild or no pain) was attained by 9 (47%) patients in the placebo group, 12 (63%) patients in the GR79236 4 microg kg-1 group, 10 (48%) patients in the 10 microg kg-1 group, and 16 (80%) patients in the diclofenac 50 mg group. Neither dose of GR79236 produced a significant improvement over placebo, but diclofenac was superior to both placebo (P=0.036) and GR79236 10 microg kg-1 (P=0.034). Median times to rescue or additional analgesia were 62, 100, 60, and 363 min for patients receiving placebo, GR79236 4 microg kg-1, 10 microg kg-1, and diclofenac 50 mg, respectively (diclofenac significantly longer than placebo, P=0.002 log-rank test). Pain control was poor in the placebo group and in both GR79236 groups, with between 79 and 86% of patients having good pain control (i.e. mild or no pain) for <20% of the time compared with only 30% of patients who received diclofenac. CONCLUSION: We found no evidence of efficacy of GR79236 compared with placebo, but the active control diclofenac was effective. It is possible that a higher dose of GR79236 might have been effective or that i.v. administration of this drug does not achieve appropriate concentrations in the brain or peripheral nerves.

A comparison of intubating conditions in children following induction of anaesthesia with propofol and suxamethonium or propofol and remifentanil.

Sixty ASA 1 and 2 children aged between 2 and 16 years who required tracheal intubation as part of anaesthesia for elective surgery were studied. We evaluated intubating conditions, haemodynamic responses and duration of apnoea following propofol 4 mg.kg-1 combined with either remifentanil 1.25 microg.kg-1 (group R), or suxamethonium 1 mg.kg-1 (group S). Tracheal intubation was graded as excellent, good or poor according to ease of laryngoscopy, vocal cord position, coughing, and jaw relaxation and limb movement. Thirty of group S and 28 of group R children were successfully intubated on the first attempt. Overall, intubation conditions were excellent or good in 26/30 (87%) patients in group S and 20/30 (67%) in group R (p<0.05). Mean apnoea time was 190 s in group S, and 362 s in group R (p<0.001). Heart rate increased in response to suxamethonium (p<0.01) and both systolic and diastolic blood pressure decreased in the remifentanil group (p<0.01).

Disseminated infection with Bartonella henselae as a cause of spontaneous splenic rupture.

A 65-year-old man developed massive hemoperitoneum secondary to spontaneous splenic rupture. Histopathological analysis of the spleen demonstrated necrotizing granulomas. Results of serological tests indicated infection with a species of Bartonella, and immunohistochemical staining established Bartonella henselae as the cause of splenitis. To our knowledge, this represents the first reported case of spontaneous splenic rupture caused by infection with a species of Bartonella.

Pulmonary cryptococcosis in the immunocompetent host. Therapy with oral fluconazole: a report of four cases and a review of the literature.

Isolated pulmonary cryptococcosis (IPC) is an infrequently diagnosed infection, the management of which is not well defined. In past years, IPC traditionally has not been treated in the immunocompetent host, given its perceived benign and self-limited course and the toxicity associated with amphotericin B. However, some patients manifest prominent and disabling symptoms, and infection occasionally may disseminate. Fluconazole is active against Cryptococcus neoformans, is easily administered, and has an excellent safety profile. We present four healthy hosts with IPC who were treated with oral fluconazole for 6 to 8 weeks. A review of the literature was conducted to identify other cases of IPC in healthy hosts who were also treated with fluconazole. Our results and the limited experience reported in the literature suggest that fluconazole may be an appropriate choice for the treatment of IPC in the immunocompetent host. Indications for treatment are not defined, but symptomatic patients, those with multiple nodules or extensive infiltrates on chest radiographs, and/or those testing positive for serum cryptococcal antigen might be potential candidates for therapy.

Cryptococcal aortitis presenting as a ruptured mycotic abdominal aortic aneurysm.

Mycotic processes occasionally complicate atherosclerotic aortic disease and usually require aggressive surgical therapy to control sepsis and prevent arterial rupture. Rarely, fungal organisms are responsible for primary infection of the abdominal aorta. We report the first case of Cryptococcal aortitis presenting as a ruptured abdominal aortic aneurysm. The surgical, pathologic, and microbiologic aspects of fungal aortitis are discussed.

Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures.

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).

Cryptococcal pneumonia complicating pregnancy.

In the present report we describe 4 previously healthy women who developed cryptococcal pneumonia during pregnancy, and 1 pregnant woman with cryptococcal meningitis. These cases illustrate a previously uncharacterized spectrum of cryptococcal disease. We also discuss 24 patients previously reported who had cryptococcal meningitis during pregnancy. Finally, we review the available data for each therapeutic option and present an algorithm for management based on appraisals of disease severity and risk to the unborn fetus. This report emphasizes the need for heightened awareness of cryptococcosis in the differential diagnosis of pneumonia, chest pain, and hypoxemia in the pregnant patient, but at present, there are insufficient epidemiologic data to determine whether incidences of pulmonary or disseminated cryptococcosis actually increase during pregnancy. The risk of congenital cryptococcosis to the unborn fetus is low, and the most likely mechanism whereby neonates acquire invasive fungal pulmonary infection is through aspiration. While it is unclear whether there is any real increased risk of spontaneous abortion or premature labor, the data indicate that overall fetal outcome depends on effective treatment of maternal infection. For patients with dense air-space consolidation, progressive pulmonary disease, or dissemination, antifungal therapy is necessary. Optimal treatment is determined by the acuity and severity of the clinical presentation. Amphotericin B (approximately 1 g) with or without flucytosine represents the choice for initial treatment of the more acutely ill patient with disseminated or progressive pulmonary cryptococcosis who requires hospitalization (whether during or after pregnancy). Oral fluconazole appears to be safe and effective alternative therapy after delivery for the less severely ill patient who can be managed on an outpatient basis. While the use of fluconazole during pregnancy generally appears safe in terms of fetal outcome (49, 58), the class C status and single report of fetal malformation (62) preclude confident recommendation for its use during pregnancy. The risks and benefits of this effective and generally less toxic drug should be discussed with the parents and weighed against the use of amphotericin B. For pregnant women with limited pulmonary cryptococcosis (segmental or nodular infiltrates) and no evidence of dissemination, we recommend close follow-up without antifungal therapy similar to the recommendation for normal hosts with minimal disease. However, it is important to note that there is no extensive experience upon which to base this recommendation for pregnant individuals (45, 55, 103, 108). It is prudent to use frequent physical examinations (for example, every 1-2 months), combined with chest roentgenograms and serum cryptococcal antigens to monitor progression and/or development of disease in both the mother and child for approximately 6 months postpartum. In conclusion, cryptococcosis during pregnancy presents a special challenge to the clinician. A balanced therapeutic approach holds great promise for successful maternal and fetal outcomes.

Evaluation of the predictive performance of a 'Diprifusor' TCI system.

The predictive performance of a 'Diprifusor' target controlled infusion system for propofol was examined in 46 patients undergoing major surgery, divided into three age groups (18-40, 41-55 and 56-80 years). Measured arterial propofol concentrations were compared with values calculated (predicted) by the target controlled infusion system. Performance indices (median performance error and median absolute performance error) were similar in the three age groups, with study medians of 16.2% and 24.1%, respectively. Mean values for 'divergence' and 'wobble' were -7.6%.h-1 and 21.9%, respectively. Measured concentrations tended to be higher than calculated concentrations, particularly following induction or an increase in target concentration. The mean (SD) propofol target concentration of 3.5 (0.7) micrograms.ml-1 during maintenance was lower in older patients, compared with higher target concentrations of 4.2 (0.6) and 4.3 (0.7) micrograms.ml-1 in the two younger age groups, respectively. The control of depth of anaesthesia was good in all patients and the predictive performance of the 'Diprifusor' target controlled infusion system was considered acceptable for clinical purposes.

Remifentanil in combination with propofol for spontaneous ventilation anaesthesia.

We have investigated the effect of four doses of remifentanil on the incidence of respiratory depression and somatic response at incision. Remifentanil was administered as a loading dose of 0.125, 0.25, 0.375 or 0.5 microgram kg-1 and at a maintenance infusion rate of 0.025, 0.05, 0.075 or 0.1 microgram kg-1 min-1, respectively, with an infusion of propofol 6 mg kg-1 h-1. Responses occurred in 88% of patients with remifentanil 0.025 microgram kg-1 min-1 compared with 30-40% in the other groups. Respiratory depression after incision increased from 6% with remifentanil 0.025 microgram kg-1 min-1 to 73% with 0.1 microgram kg-1 min-1. Increases in propofol infusion rate to 7.2-8.4 mg kg-1 h-1 produced adequate maintenance of anaesthesia. Reductions in remifentanil doses to 0.025-0.05 microgram kg-1 min-1 resulted in adequate respiration at the end of surgery in 88% of patients. Maintenance infusions of the two drugs for spontaneous ventilation are likely to be in these ranges. However, the ideal loading doses and infusion rates for induction remain to be established.

A randomized, prospective, blinded comparison of postoperative pain, metabolic response, and perceived health after laparoscopic and small incision cholecystectomy.

BACKGROUND: We have previously shown that in a randomized comparison of laparoscopic (LC) versus small incision (SC) cholecystectomy, postoperative hospital stay is comparable. This randomized prospective study compares the postoperative pain, analgesic and antiemetic consumption, perceived health, and metabolic and respiratory responses after these two procedures. METHODS: Two hundred patients were recruited; postoperative stay, pain scores, analgesic and antiemetic consumption were recorded. Nottingham Health Profile questionnaires were completed by a subgroup of 100 patients, and the metabolic and respiratory responses were also compared in a further subgroup of 20 patients. RESULTS: Pain scores in both groups were low. LC, however, was associated with lower postoperative pain scores and analgesic requirements compared with SC, but the antiemetic requirements were greater after LC. The duration of hospital stay and the perceived health after operation were the same in both groups, and both procedures were associated with a similar reduction of respiratory function. Twenty-four hours after operation the inflammatory (C-reactive protein, CRP) response to LC (22 +/- 20 mg/L) was significantly lower than after SC (68 +/- 30 mg/L), but the neuroendocrine (cortisol) response was similar (LC, 475 +/- 335 nmol/L, compared with SC, 710 +/- 410 nmol/L). Independent of the technique used, the duration of postoperative hospital stay correlated significantly with the magnitude of both the 24-hour postoperative cortisol and CRP responses (cortisol: rs = 0.678, p < 0.001; CRP: rs = 0.566, p = 0.011). CONCLUSIONS: LC appears to be associated with less tissue destruction and pain than SC, but this did not confer any advantage in the degree of postoperative respiratory impairment, length of hospital stay, or postoperative perceived health. The neuroendocrine component of the metabolic response evoked by each procedure was similar and had a significant correlation to patient's postoperative hospital stay. This finding may explain the similar postoperative recovery after LC and SC.

Propofol infusion vs thiopentone/isoflurane anaesthesia for prominent ear correction in children.

Postoperative nausea and vomiting (PONV) frequently follows prominent ear correction under general anaesthesia in children. In a prospective, single-blind study, we compared the incidence of PONV after propofol infusion anaesthesia with that following thiopentone induction and isoflurane maintenance in 30 children aged from four to 14 years randomly allocated to one of two groups. All the children were mechanically ventilated. Anaesthesia was supplemented in both groups with nitrous oxide and infiltration of the ears using a mixture of bupivacaine, adrenaline, and hyaluronidase. One child receiving propofol (group P) complained of nausea, compared with eight receiving thiopentone/ isoflurane, (group T) (P = 0.005), while three children in group P and ten in group T vomited before hospital discharge, (P = 0.01). Eight children in group P were considered to be fit for discharge on the day of surgery as against four in group T, (not significant). Only four out of twelve children receiving opioid analgesia vomited.

The influence of alfentanil pre-treatment on ventilatory effects of doxapram following induction of anaesthesia with propofol.

BACKGROUND: Hypoventilation may occur following induction of anaesthesia with propofol and is potentiated by concurrent use of opioid drugs. This effect is undesirable in patients who will continue to maintain spontaneous respiration during anaesthesia and surgery. The analeptic drug doxapram is known to have selective respiratory stimulatory effects but its action during induction of anaesthesia has been inconsistent. METHOD: In a double-blind, placebo-controlled study, the influence of alfentanil pre-treatment on the ventilatory effects of doxapram given during induction of anaesthesia with propofol was studied in 40 patients. Four groups of ten patients (two groups pre-treated with 7 micrograms.kg-1 of alfentanil and two groups with saline) were randomly allocated to receive either 0.5 mg.kg-1 doxapram or saline following infusion of propofol to loss of verbal contact. RESULTS: In the groups that received doxapram, minute volumes were significantly increased and end-tidal carbon dioxide concentrations were significantly reduced compared to control groups, although the duration and extent of these effects were less in the group that received alfentanil. Doxapram also reversed an alfentanil-induced reduction in respiratory rate. No adverse cardiovascular or neurological stimulatory effects of doxapram were evident at any time. CONCLUSION: We conclude that doxapram 0.5 mg.kg-1 is effective in augmenting ventilation that has been obtunded following induction of anaesthesia with propofol in patients pre-treated with alfentanil.

Reactivation toxoplasmic retinochoroiditis in patients undergoing bone marrow transplantation: is there a role for chemoprophylaxis?

The objective of this study was to report the occurrence of reactivation ocular toxoplasmosis in bone marrow transplant (BMT) recipients and to propose guidelines for identification and chemoprophylaxis of high-risk patients. The study design was a series of cases from the tertiary care university hospital which has an active BMT program. The patients were two recipients of autologous BMTs with past histories of toxoplasma retinochoroiditis who developed symptomatic reactivation of ocular toxoplasmosis as documented by formal opthalmologic examination in the early post-transplant period. Opthalmoscopic examinations in the two patients with non-Hodgkin's lymphoma who received autologous transplants and then developed decreased visual acuity in the first week after transplant revealed recurrent retinochoroiditis adjacent to old toxoplasma lesions. Pre-transplant eye examinations in both patients had demonstrated only inactive chorioretinal scars. Therapy with sulfadiazine, pyrimethamine and prednisone ultimately led to resolution of retinitis in both patients. BMT recipients who are seropositive for antibody to T. gondii and have findings consistent with previous toxoplasma retinochoroiditis on pre-transplant ophthalmologic examination appear to be at risk for reactivation of ocular toxoplasmosis in the early post-transplant period and may warrant preventive chemoprophylaxis for toxoplasmosis.

Changes in intra-ocular pressure during general anaesthesia. A comparison of spontaneous breathing through a laryngeal mask with positive pressure ventilation through a tracheal tube.

Changes in-intra-ocular pressure during spontaneous ventilation with a laryngeal mask were compared with controlled ventilation using a tracheal tube in 40 patients undergoing intra-ocular surgery under general anaesthesia. Intra-ocular pressure was measured before induction, after establishing the airway, at the end of the operation and after removal of the airway device. Anaesthesia was induced with propofol and maintained with enflurane and nitrous oxide in oxygen. Mean end-tidal carbon dioxide tension was significantly higher during spontaneous ventilation than during controlled ventilation 5 min after establishing the airway (5.7 versus 4.5) and at the end of surgery (6.1 versus 4.2) (p < 0.001). Despite this, intra-ocular pressures were lower than baseline and similar in the two groups throughout anaesthesia. At the end of surgery, intra-ocular pressure (mmHg) was 11.2 and 8.6 during spontaneous or controlled ventilation respectively. One min after removal of the device, mean intra-ocular pressure (mmHg) in the tracheal tube group (16.0) was slightly higher than baseline (15.3) and was significantly higher than the laryngeal mask group (10.9) (p < 0.01). Spontaneous ventilation with a laryngeal mask is an acceptable alternative to controlled ventilation with tracheal intubation in elective intra-ocular surgery.

Infectious emergencies in patients with diabetes mellitus.

Although it remains controversial as to whether diabetics have an overall increased incidence of infection as compared to nondiabetics, several potentially life-threatening infections do appear to be uniquely associated with diabetes. These infections generally occur in older diabetics with less than optimal glucose control. For each entity, selected symptoms and signs may suggest the diagnosis but confirmation of via tissue biopsy with culture and histopathology or radiography is usually necessary. Management typically require both antimicrobial treatment and surgery.

Myocardial ischaemia during tracheal intubation and extubation.

The incidence of myocardial ischaemia during tracheal intubation and extubation was compared using ambulatory ECG monitoring in 60 patients undergoing a variety of different surgical operations. Seven patients had myocardial ischaemia after tracheal intubation and seven patients during tracheal extubation. The patients who developed myocardial ischaemia during tracheal extubation had significantly greater rate-pressure products immediately before tracheal extubation (P < 0.05) and 1 min after tracheal extubation (P < 0.01) compared with those patients who did not develop myocardial ischaemia during extubation.

Disposition of milrinone in patients after cardiac surgery.

We have evaluated the disposition of milrinone in seven patients with low cardiac output after elective cardiac surgery involving cardiopulmonary bypass. Patients received a loading dose of milrinone 50 micrograms kg-1 given over 10 min followed immediately by an infusion of 0.5 microgram kg-1 min-1, continued for a minimum of 5 h. Plasma concentrations of milrinone were measured at designated intervals during the infusion and for 6 h after its termination, by high pressure liquid chromatography. Concentrations greater than 100 ng ml-1 were produced in all patients within 2 min of starting the loading dose and were maintained for the duration of the infusion. Volume of distribution, clearance and terminal half-life were similar to those found in patients with chronic cardiac failure.

Combined infusions of morphine and ketamine for postoperative pain in elderly patients.

The value of using a combined infusion of morphine with a variable dose of ketamine for postoperative analgesia following upper abdominal surgery was assessed in a double-blind randomised study of 40 elderly patients. Four groups of 10 patients received an infusion of morphine at 1 mg.h-1, either alone, or combined with ketamine at a rate of 5, 10 or 20 mg.h-1. The addition of ketamine to a continuous infusion of morphine did not significantly improve either analgesia or postoperative lung function. Increasing the dose of ketamine resulted in an increased incidence of postoperative dreaming (p < 0.01).

Rapid intravenous infusion of amphotericin B: a pilot study.

PURPOSE: The administration of amphotericin B in the conventional prolonged infusion over 4 to 6 hours is complicated by the acute toxicities of fevers and chills in 50% to 90% of patients and the chronic toxicities of increased creatinine levels and hypokalemia in 60% to 80% of patients. To determine the safety and toxicity of rapid infusions, we conducted a prospective, nonrandomized study in patients with clinical indications for antifungal therapy. PATIENTS AND METHODS: Twenty-five granulocytopenic adults with acute leukemia and myelodysplastic syndromes were enrolled in a phase I trial using four sequentially shorter infusion durations: a standard infusion over 4 hours (n = 3) and shortened infusion durations at 3 hours (n = 3), 2 hours (n = 4), and 1 hour (n = 15). Toxicity was assessed by daily examinations of study subjects by one of the study investigators, by documentation of all infusion-related fevers and chills, and by daily monitoring of serum levels of creatinine, potassium, magnesium, and aspartate aminotransferase. RESULTS: Temperatures greater than 38 degrees C occurred in 16 of 25 (64%) patients, but only two had temperatures exceeding 40 degrees C. Chills were observed in 13 of 25 (56%) patients, but only one had severe symptoms. Serum creatinine increased more than 0.5 mg/dL (44.20 mumol/L) above the pretreatment baseline in 17 of 25 (68%) patients, and the absolute creatinine level was greater than or equal to 2.0 mg/dL (176.8 mumol/L) in 10 of 25 (40%) patients. Serum potassium levels dropped below the normal limit of 3.5 mEq/L (3.5 mmol/L) in all patients, but no patient had potassium levels below 2.5 mEq/L (2.5 mmol/L). Intravenous potassium supplementation was administered to all patients and exceeded 100 mEq/d in 12 of 25 (48%) patients. CONCLUSIONS: Rapid infusions of amphotericin B are safe, are associated with similar toxicity as prolonged infusions, and facilitate inpatient care by decreasing nursing time needed for administration and minimizing scheduling conflicts with other necessary intravenous medications. Shorter infusions also facilitate outpatient and home administration of amphotericin B.