Disruptions of functional connectivity in the default mode network of comatose patients.

OBJECTIVE: To evaluate the possible role of the default mode network (DMN) in consciousness and assess the diagnostic or prognostic potential of DMN connectivity measures in the assessment of a patient group lacking cognitive awareness. METHODS: DMN connectivity was established using independent component analysis of resting-state fMRI data in patients with reversible (n = 2) and irreversible (n = 11) coma following cardiac arrest and compared to healthy controls (n = 12). RESULTS: A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness. CONCLUSIONS: The results suggest that the DMN is necessary but not sufficient to support consciousness. Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.

Myoclonic status epilepticus following repeated oral ingestion of colloidal silver.

The authors report a case of a 71-year-old man who developed myoclonic status epilepticus and coma after daily ingestion of colloidal silver for 4 months resulting in high levels of silver in plasma, erythrocytes, and CSF. Despite plasmapheresis, he remained in a persistent vegetative state until his death 5.5 months later. Silver products can cause irreversible neurologic toxicity associated with poor outcome.

Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis.

Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability (; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NO(x)) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NO(x) increased 254% (P < 0.05), stopped flow capillaries increased 149% (P < 0.05), and decreased 12.7% (P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NO(x), accumulation of HbNO, and decreases in both and functional CD. We found no evidence of leukocyte plugging postcapillary venules. Our findings suggest that decreased functional CD during sepsis resulted from a NO-mediated decrease in erythrocyte deformability.

Comparison of open, percutaneous, and translaryngeal tracheostomies.

INTRODUCTION: With 3 tracheostomy techniques currently available, controversy exists regarding which is safest and most economical. Percutaneous (PDT) and the new translaryngeal (TLT) tracheostomies are cited as more cost-effective than the traditional open surgical procedure because they are bedside techniques. Our objective was to compare the perioperative and postoperative complications of the 3 techniques. STUDY DESIGN: This was a prospective trial involving 100 consecutive patients who underwent tracheostomy between April and December of 1997 at the London Health Sciences Centre and St Joseph's Health Centre in London, Canada. RESULTS: Fifty open tracheostomies were performed. Indications included prolonged ventilation (n = 42), airway protection (n = 5), pulmonary hygiene (n = 2), and sleep apnea (n = 1). A tension pneumothorax was the one significant intraoperative complication. Fifteen postoperative complications occurred, most notable of which was a 2-L hemorrhage at 24 hours. Thirty-seven TLTs were performed, 20 in patients with coagulopathy. Indications were prolonged intubation (n = 27), airway protection (n = 9), and pulmonary hygiene (n = 1). One intraoperative complication of accidental decannulation occurred. One postoperative complication, a pretracheal abscess, occurred in a decannulated transplant patient 2 weeks after the procedure. Thirteen PDTs were performed. Indications were prolonged intubation (n = 6), airway protection (n = 6), and tracheal toilet (n = 1). No significant complications occurred. CONCLUSIONS: TLT and PDT have fewer complications than the traditional open technique. TLT appears to have the greatest utility in the coagulopathic patient.

Effect of subarachnoid morphine administration on extubation time after coronary artery bypass graft surgery.

OBJECTIVE: To determine the effects of 2 low doses of intrathecal morphine on extubation time and on postoperative analgesic requirements after coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Fifty adult patients scheduled for elective primary CABG surgery. INTERVENTIONS: Patients were randomized to receive placebo, 250 microg, or 500 microg intrathecal morphine, preoperatively. Intraoperative fentanyl and midazolam were limited to 15 microg/kg and 20 microg/kg intravenously. Patients were extubated in the intensive care unit by a blinded observer using predefined extubation criteria. MEASUREMENTS AND MAIN RESULTS: Time to extubation and postoperative requirements for morphine, midazolam, nitroglycerin, and sodium nitroprusside were recorded by a blinded observer. Extubation times were 441 +/- 207 minutes versus 325 +/- 188 minutes versus 409 +/- 245 minutes for the placebo, 250-microg, and 500-microg groups (p = 0.27). Postoperative morphine requirements in the 250-microg and 500-microg groups were 13.6 +/- 7.8 mg and 11.7 +/- 7.4 mg, compared with 21.3 +/- 6.2 mg in the placebo group (p = 0.001). There were no differences among the study groups with regard to postoperative midazolam, nitroglycerin, and sodium nitroprusside requirements. CONCLUSIONS: Despite decreased postoperative morphine requirements, intrathecal morphine administration did not have a clinically relevant effect on extubation time after CABG surgery. This study suggests that 250 microg is the optimal dose of intrathecal morphine to provide significant postoperative analgesia without delaying tracheal extubation.

Hepatotoxicity possibly caused by amphotericin B.

OBJECTIVE: To report a case of possible amphotericin B-induced hepatotoxicity in a patient with pulmonary blastomycosis. SUMMARY: A 26-year-old white man with life-threatening pulmonary blastomycosis developed elevation of his liver enzymes after the addition of amphotericin B to his initial itraconazole therapy. The hepatotoxicity resolved rapidly with discontinuation of the amphotericin B, and the blastomycosis was successfully treated with itraconazole alone. DISCUSSION: This case illustrates an unusual occurrence of hepatotoxicity associated with a short course of amphotericin B. Liver biopsy was compatible with drug-induced changes and showed no evidence of blastomycosis. Discontinuation of amphotericin B with no other therapeutic changes resulted in a rapid resolution of hepatotoxicity. A possible adverse drug interaction with itraconazole and amphotericin B is postulated based on the mechanism of action of each drug. CONCLUSIONS: Amphotericin B therapy can be associated with many adverse effects, but reports of hepatotoxicity are rare. Closer monitoring of liver enzymes in patients receiving amphotericin B, especially in combination with potentially hepatotoxic agents, including azole antifungal drugs, would be prudent.

Sevoflurane has no effect on sinoatrial node function or on normal atrioventricular and accessory pathway conduction in Wolff-Parkinson-White syndrome during alfentanil/midazolam anesthesia.

BACKGROUND: The effects of sevoflurane on the electrophysiologic properties of the human heart are unknown. This study evaluated the effects of sevoflurane on the electrophysiologic properties of the normal atrioventricular conduction system, and on the accessory pathways in patients with Wolff-Parkinson-White syndrome, to determine its suitability as an anesthetic agent for patients undergoing ablative procedures. METHODS: Fifteen patients with Wolff-Parkinson-White syndrome undergoing elective radiofrequency catheter ablation were studied. Anesthesia was induced with alfentanil (20-50 microg/kg) and midazolam (0.15 mg/kg), and vecuronium (20 mg) and maintained with alfentanil (0.5 to 2 microg x kg(-1) x min(-1)) and midazolam (1 or 2 mg every 10-15 min, as required). An electrophysiologic study measured the effective refractory period of the right atrium, atrioventricular node, and accessory pathway; the shortest conducted cycle length of the atrioventricular node and accessory pathway during atrial pacing; the effective refractory period of the right ventricle and accessory pathway; and the shortest retrograde conducted cycle length of the accessory pathway during ventricular pacing. Parameters of sinoatrial node function included sinus node recovery time, corrected sinus node recovery time, and sinoatrial conduction time. Intraatrial conduction time and the atrial-His interval were also measured. Characteristics of induced reciprocating tachycardia, including cycle length, atrial-His, His-ventricular, and ventriculoatrial intervals, also were measured. Sevoflurane was administered to achieve an end-tidal concentration of 2% (1 minimum alveolar concentration), and the study measurements were repeated. RESULTS: Sevoflurane had no effect on the electrophysiologic parameters of conduction in the normal atrioventricular conduction system or accessory pathway, or during reciprocating tachycardia. However, sevoflurane caused a statistically significant reduction in the sinoatrial conduction time and atrial-His interval but these changes were not clinically important. All accessory pathways were successfully identified and ablated. CONCLUSIONS: Sevoflurane had no effect on the electrophysiologic nature of the normal atrioventricular or accessory pathway and no clinically important effect on sinoatrial node activity. It is therefore a suitable anesthetic agent for patients undergoing ablative procedures.

Intraaortic balloon counterpulsation improves right ventricular failure resulting from pressure overload.

BACKGROUND: Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload. METHODS: In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres. RESULTS: After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 +/- 2 to 60 +/- 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 +/- 4 to 49 +/- 2 mm Hg; p < 0.01), RV ejection fraction (0.51 +/- 0.04 to 0.16 +/- 0.02; p < 0.01), and cardiac index (2.48 +/- 0.04 to 1.02 +/- 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 +/- 2 to 61 +/- 3 mm Hg; p < 0.01), cardiac index (1.02 +/- 0.11 to 1.45 +/- 0.14; p < 0.05), RV ejection fraction (0.16 +/- 0.02 to 0.23 +/- 0.02; p < 0.01), and blood flow to the left ventricle. CONCLUSIONS: In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.

Bacterial meningitis and cauda equina syndrome after epidural steroid injections.

PURPOSE: To describe a rare adverse outcome resulting from lumbar epidural steroid injections for the treatment of chronic lower back pain. CLINICAL FEATURES: We report a case of staphylococcus aureus meningitis and cauda equina syndrome following a series of epidural steroid injections for chronic back pain. Although rare, bacterial meningitis following epidural analgesia has been reported, but epidural steroid injections have not been associated with either bacterial meningitis or cauda equina syndrome. The causal relationship between epidural steroid injections, bacterial meningitis, and cauda equina syndrome is discussed. CONCLUSION: A through pre-procedure assessment with attention to the neurologic examination and signs/symptoms of infection is essential.

High-dose vecuronium neuromuscular block: a comparison of arrhythmias and onset of block during sufentanil anaesthesia.

This study compared the heamodynamic effects of sufentanil with those observed following concomitant sufentanil and high-dose vecuronium administration to determine whether vecuronium induces bradyarrhythmias. Sixty coronary artery bypass patients were stratified into beta blocker (n = 30) or non-beta blocker (n = 30) groups and following induction with sufentanil (9 +/- 3 micrograms.kg-1) and midazolam (0.07 +/- 0.04 mg.kg-1), received either succinylcholine 1 mg.kg-1 (SxCh), vecuronium 0.3 mg.kg-1 (Vec 0.3), or vecuronium 0.5 mg.kg-1 (Vec 0.5). Using a Holter ECG monitor, bradyarrhythmias were classified as mild (HR 46-50), moderate (HR 40-45) or severe (HR < 40). In the pre-induction period, there were no differences in the incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or Vec 0.5 groups, in either the beta blocker or non-beta blocker groups. Following induction, there were similar reductions in mean heart rate and mean arterial pressure in all three muscle relaxant groups in both the beta and the non-beta blocker groups; however, there was no difference in the incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or Vec 0.5 groups. The Vec 0.5 beta blocker group had a higher incidence of mild bradyarrhythmias (32 +/- 36%) than the Vec 0.5 non-beta blocker group (2 +/- 3%, P = 0.017). Using EMG recording, the onset time of maximal neuromuscular block for the Vec 0.3 group (108 +/- 17 sec) was longer (P < 0.05) than the SxCh (76 +/- 21 sec) and Vec 0.5 (82 +/- 13 sec) groups, which were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Propofol has no direct effect on sinoatrial node function or on normal atrioventricular and accessory pathway conduction in Wolff-Parkinson-White syndrome during alfentanil/midazolam anesthesia.

BACKGROUND: Propofol has been implicated as causing intraoperative bradyarrhythmias. Furthermore, the effects of propofol on the electrophysiologic properties of the sinoatrial (SA) node and on normal atrioventricular (AV) and accessory pathways in patients with Wolff-Parkinson-White syndrome are unknown. Therefore, this study examined the effects of propofol on the cardiac electrophysiologic properties in humans to determine whether propofol promotes bradyarrhythmias and its suitability as an anesthetic agent in patients undergoing ablative procedures. METHODS: Twelve patients with Wolff-Parkinson-White syndrome undergoing radiofrequency catheter ablation were studied. Anesthesia was induced with alfentanil (50 micrograms/kg), midazolam (0.15 mg/kg), and vecuronium (20 mg) and maintained with alfentanil (2 micrograms.kg-1.min-1) and midazolam (1-2 mg, every 15 min, as needed). A electrophysiologic study was performed consisting of measurement of the effective refractory period of the right atrium, AV node, and accessory pathway and the shortest cycle length of the AV node and accessory pathway during antegrade stimulation plus the effective refractory period of the right ventricle and accessory pathway and the shortest cycle length of the accessory pathway during retrograde stimulation. Determinants of SA node function including sinus node recovery time, corrected sinus node recovery time, and SA conduction time; intraatrial conduction time and atrial-His interval also were measured. Reciprocating tachycardia was induced by rapid right atrial or ventricular pacing, and the cycle length and atrial-His, His-ventricular, and ventriculoatrial intervals were measured. Alfentanil/midazolam was then discontinued. Propofol was administered (bolus 2 mg/kg + 120 micrograms.kg-1.min-1), and the electrophysiologic measurements were repeated. RESULTS: Propofol caused a statistically significant but clinically unimportant prolongation of the right atrial refractory period. The effective refractory periods of the AV node, right ventricle, and accessory pathway, as well as the shortest cycle length, were not affected. Parameters of SA node function and intraatrial conduction also were not affected. Sustained reciprocating tachycardia was inducible in 8 of 12 patients, and propofol had no effect on its electrophysiologic properties. All accessory pathways were successfully identified and ablated. CONCLUSIONS: Propofol has no clinically significant effect on the electrophysiologic expression of the accessory pathway and the refractoriness of the normal AV conduction system. In addition, propofol has no direct effect on SA node activity or intraatrial conduction; therefore, it does not directly induce bradyarrhythmias. It is thus a suitable agent for use in patients undergoing ablative procedures who require either a neuroleptic or general anesthetic.

Flumazenil as a diagnostic tool in the differential diagnosis of coma in a critically ill patient.

The purpose of this report is to describe the use of flumazenil as a diagnostic aid in the differential diagnosis of coma in a patient with an inadvertent overdose of benzodiazepines. We report a patient with suspected septic encephalopathy whose level of consciousness markedly improved following flumazenil administration. Subsequent analysis revealed the presence of benzodiazepines and their metabolites in the blood and urine although the patient had not received benzodiazepines for over two weeks. The critically ill patient with multiorgan failure may have considerable derangement of benzodiazepine metabolism; therefore, if an obtunded patient's level of consciousness improves following flumazenil administration, benzodiazepine intoxication must be considered.

The electrophysiologic effects of volatile anesthetics and sufentanil on the normal atrioventricular conduction system and accessory pathways in Wolff-Parkinson-White syndrome.

BACKGROUND: The effects of volatile agents and sufentanil anesthesia on the electrophysiologic properties of the accessory pathway and on the incidence of intraoperative tachyarrhythmias in patients with Wolff-Parkinson-White syndrome are unknown. Therefore, we studied these agents for their use in patients undergoing ablative procedures or requiring a general anesthetic for other surgeries. METHODS: Twenty-one patients with Wolff-Parkinson-White syndrome undergoing surgical ablation were anesthetized with sufentanil (20 micrograms/kg), lorazepam (0.06 mg/kg), and vecuronium (20 mg). After sternotomy, the electrophysiologic study during antegrade stimulation consisted of the effective refractory period of the right atrium, atrioventricular node, and accessory pathway; the shortest cycle length of the atrioventricular node and accessory pathway; and the coupling interval. During retrograde stimulation, the effective refractory period of the right ventricle and accessory pathway and the shortest cycle length of the accessory pathway were measured and compared to preoperative electrophysiologic values. Patients then were randomized to receive 1 MAC of halothane, isoflurane, or enflurane, and the electrophysiologic study was repeated. RESULTS: Sufentanil-lorazepam caused mild prolongation (P < 0.05) of the effective refractory period of the accessory pathway and the shortest cycle length of the atrioventricular node. Enflurane and isoflurane significantly prolonged all parameters related to refractoriness during antegrade conduction, with enflurane having the largest effect. During retrograde conduction, isoflurane prolonged the effective refractory period of the right ventricle and accessory pathway and the shortest cycle length of the accessory pathway, whereas enflurane prolonged only the accessory pathway effective refractory period and shortest cycle length. Halothane had the least effect on refractoriness, causing significant prolongation of the atrioventricular node effective refractory period and the shortest cycle length of the accessory pathway only during antegrade conduction. The coupling interval, a measure of the period of vulnerability to supraventricular tachycardia, was prolonged only by halothane and isoflurane. Supraventricular tachycardia was still obtainable in all patients. CONCLUSIONS: Sufentanil-lorazepam has no clinically significant effect on the electrophysiologic expression of the accessory pathway. Of the volatile agents, enflurane most, isoflurane next, and halothane least increased refractoriness within the accessory and atrioventricular pathways. Therefore, administration of these volatile agents during ablative procedures may confound interpretation of postablative studies used to determine the success of ablation treatment. Conversely, in patients with preexcitation syndrome requiring general anesthesia for nonablative procedures, volatile agents may reduce the incidence of perioperative tachyarrhythmias because of their effects on refractoriness. Enflurane would be the agent of choice because it increases refractoriness the most without prolonging the coupling interval.

The use of muscle relaxants in the intensive care unit.

Neuromuscular blocking agents are frequently used in the Intensive Care Unit to facilitate tracheal intubation and the application of continuous paralysis. This review will focus on various conditions of the critically ill patient such as multi-organ dysfunction, acid-base and electrolyte imbalance, prolonged immobility, multiple drug interactions and specific disease/injury processes that may affect the pharmacokinetic and pharmacodynamic behaviour of muscle relaxants. As such, due to the complex nature of the critically ill patients, the effects of neuromuscular blocking agents are unpredictable. Therefore, guidelines regarding their administration and the methodology and requirement for continuous bedside monitoring of neuromuscular function will be presented.

Alfentanil-midazolam anaesthesia has no electrophysiological effects upon the normal conduction system or accessory pathways in patients with Wolff-Parkinson-White syndrome.

The effects of alfentanil-midazolam anaesthesia upon the electrophysiologic (EP) properties of normal atrioventricular (A-V) and accessory pathway (AP) conduction were studied in eight patients with Wolff-Parkinson-White syndrome during accessory pathway surgical ablation. The presence of an AP was confirmed by preoperative EP studies. Anaesthesia was induced with alfentanil (50 micrograms.kg-1) and midazolam (0.15 mg.kg-1) and maintained with an alfentanil infusion (2 micrograms.kg-1.min-1) and intermittent boluses of midazolam (1-2 mg q 15 min, PRN). Following sternotomy, a baseline EP study was performed which consisted of effective refractory period (ERP) and shortest cycle length (SCC) measurement during antegrade conduction in the AV and AP, as well as during retrograde conduction in the AP. Comparison with preoperative EP studies indicated that the administration of alfentanil-midazolam anaesthesia had no effect upon conduction or ERP in either pathway. Haemodynamic stability occurred throughout the surgical procedure with no tachyarrhythmias. We conclude that a combination of alfentanil-midazolam is suitable for general anaesthesia in patients undergoing ablative procedures for accessory pathways.