Carfentanil on the darknet: Potential scam or alarming public health threat?

BACKGROUND: In an age of global insecurity, highly potent synthetic drugs have become a major public health issue. Their online advertisement and sale are facilitated by surface web, darknet markets and social media fuelling substance abuse and addiction, as well as various types of new criminal activities and their growth in sophistication. This study presents a systematic analysis of the darknet sale of one of the most potent synthetic opioids: Carfentanil. With an equianalgesic potency of 10.000 times a unit of morphine, its toxicity is comparable to traditional nerve agents, and it has been previously used as a chemical weapon, causing human fatalities. METHODS: Digital trace data was collected retrospectively from all the darknet marketplaces, which have been active in the past five years. Data on vendors offering Carfentanil on Agartha, Empire and Yakuza marketplaces were analysed with regard to items sold and sellers' features as these were the only active markets at the time of search. Searches were carried out in the English language only. RESULTS: 63 Cartfentanil vendors operating on 19 darknet marketplaces were identified. Contacts and payments were facilitated with end-to-end encryption messaging mobile applications and content-expiring messages. Although it is known that Agartha is a scam market, and no operative sellers were found on Yakuza, several sellers promoting Carfentanil sales were active in the Empire marketplace with a number of transaction ranging from 4 to 1223. CONCLUSION: The availability of highly potent drugs such as Carfentanil on the darknet requires the urgent development of novel scientific methods and tools able to monitor and to predict such new threats, while informing policymaking and protecting the health and the security of citizens.

An evaluation of a new two-electrode myocardial electrical impedance monitor for detecting myocardial ischemia.

The objective of this study was to determine the efficacy of a two-electrode myocardial electrical impedance (MEI) monitor in reproducibly detecting induced myocardial ischemia by comparing MEI changes with hemodynamic changes, including sonomicrometric changes. With institutional approval, 80 dogs were anesthetized with sodium thiamylal, intubated, ventilated, and had venous, arterial, and pulmonary artery catheters placed. Medial sternotomy was performed to facilitate myocardial exposure and allow the left anterior descending coronary artery (LAD) to be isolated. Two pacing electrodes were attached to the myocardium to measure MEI with a monitor. Seventy dogs were randomly assigned to the 15, 30, 45, 60, or 120 min LAD occlusion group. Sonomicrometric transducers were attached to the myocardium of the ten remaining dogs and their LAD was occluded for 36 min. MEI increased immediately after LAD occlusion to a level significantly more (P < 0.05) than baseline and returned to the baseline level upon reperfusion. Twenty dogs developed ventricular fibrillation with no attempts at resuscitation. MEI changes paralleled the sonomicrometric changes expected with ischemia. No significant cardiovascular hemodynamic changes were found with less than 45 min of LAD occlusion. Sixty and 120 min LAD occlusion resulted in significant decreases in cardiac output. The results of these experiments demonstrate that the two-electrode MEI monitor reproducibly changes in response to myocardial ischemia.

Comparative effects of oral clonidine and intravenous esmolol in attenuating the hemodynamic response to epinephrine injection.

STUDY OBJECTIVE: To evaluate oral clonidine and intravenous esmolol in blunting hemodynamic changes associated with intranasal injection of an epinephrine-containing local anesthetic solution during general anesthesia. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University Medical Center. PATIENTS: 61 consenting ASA physical status I and II outpatients undergoing endoscopic sinus and septoplasty surgery with general anesthesia. INTERVENTIONS: All patients were assigned to receive either a placebo (P) tablet or a similar-appearing tablet containing either clonidine 0.2 mg (C2) or 0.4 mg (C4) orally 1 hour prior to entering the operating room. Prior to the intranasal injection of epinephrine, patients were administered either saline, 0.03 ml.kg-1 followed by an infusion of 0.016 ml.kg-1.min-1, or esmolol (E) 300 micrograms.kg-1 followed by a continuous infusion of 160 micrograms.kg-1.min-1. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure and heart rate (HR) values were recorded preoperatively, immediately before induction of anesthesia, and at 1-minute intervals after induction of anesthesia until 15 minutes after injection of an epinephrine-containing solution. Level of sedation was assessed using a linear visual analog scale (VAS) prior to oral premedication, immediately before induction of anesthesia, and 30 minutes after anesthesia. There were no significant differences in sedation scores among the four treatment groups. HR following injection of epinephrine-containing solution was significantly less in the C2, C4, and E groups than the placebo group. Compared to P and E treatment groups, MAP values were significantly lower in the C4 treatment group. CONCLUSION: In this healthy, young, nonsmoking outpatient population, premedication with oral clonidine, 0.2 to 0.4 mg, was effective in blunting the acute hemodynamic changes associated with injection of an epinephrine-containing local anesthetic solution during endoscopic sinus or septoplasty surgery.

The effects of verapamil and diltiazem pretreatment on potassium release in dogs after the administration of succinylcholine.

UNLABELLED: Verapamil exacerbates the increase in serum potassium after a large-dose potassium infusion or after the IV administration of succinylcholine. We conducted a study in 12 canines conditioned for 30 days acting as their own controls. The canines had chronic tracheotomies and carotid loops performed 2 wk before the experiment. Control canines were given 1 mg/kg succinylcholine at Time 0. Blood samples were analyzed for potassium at 0, 1, 3, 5, 10, 15, 30, and 60 min. One week later, the dogs received 0.15 mg/kg of either verapamil or diltiazem, followed by a 5.6-microg x kg(-1) x min(-1) 10-min infusion of the same drug. The animals were then given a bolus dose of succinylcholine 1 mg/kg, and the blood potassium was analyzed as before. There was no significant difference in the potassium concentration before the succinylcholine injection (Time 0) between the study groups. The canines pretreated with verapamil had a significantly greater increase (24% +/- 8%) in potassium concentration than the control canines (14% +/- 6%) 15 min after succinylcholine administration. There was no difference between the potassium concentrations of the diltiazem-pretreated canines and the control group at any time point. Therefore, diltiazem pretreatment does not significantly influence potassium regulation after a succinylcholine injection, whereas verapamil pretreatment has measurable hyperkalemic effects. IMPLICATIONS: Succinylcholine is a drug that causes blood potassium to increase. Potassium influences heart rhythm. Verapamil and diltiazem are drugs used for angina heart pain. We used dogs to determine the effect of verapamil or diltiazem on the blood's potassium after an injection of succinylcholine and found that verapamil had the greatest effect.

A comparison of isoflurane versus fentanyl as primary anesthetics for mitral valve surgery.

We conducted a randomize study of fentanyl compared to isoflurane anesthesia in patients with pulmonary hypertension undergoing mitral valve surgery. Patients were premedicated and randomly assigned to one of two groups: 21 patients had anesthesia induced with thiopental and maintained with isoflurane; 23 patients had anesthesia induced with a fentanyl bolus and maintained with a fentanyl infusion. Adjustments of fentanyl infusion and isoflurane concentration, as well as fentanyl boluses and vasoactive/positive inotropic medication, were administered to maintain preoperative arterial blood pressure. Both groups exhibited similar demographics, similar duration of cardiopulmonary bypass (CPB) surgery, anesthesia, and time from entrance into the surgical intensive care unit (SICU) to endotracheal extubation. However, the time from entrance into the SICU to awake was significantly (P < 0.05) shorter in patients given isoflurane anesthesia. Hemodynamic variables were recorded at baseline and 12 surgical events and compared between and within groups. Significant changes from baseline were demonstrated in both groups upon institution and discontinuation of CPB. Patients receiving isoflurane anesthesia exhibited cardiovascular depression as compared to their baseline. There were no deaths in either patient group. Adequate hemodynamic profiles were achieved in both groups with comparable use of inotropic and vasoactive medication, with the exception of norepinephrine that was administered intraoperatively to significantly (P < 0.05) more patients in the isoflurane-based anesthesia group. Neither technique was associated with acute improvement of right heart performance or pulmonary hypertension, in large part because of morphologic changes of the pulmonary arterial bed, occurring with long-standing mitral valve disease. We conclude that isoflurane-based anesthesia is adequate for this type of surgery, although there is a higher anesthetic algorithm failure rate than with fentanyl-based anesthetic technique.

The effect of right internal jugular vein cannulation on intracranial pressure.

Access to the central venous circulation is often necessary in patients who have elevated intracranial pressure. It has been suggested that a disadvantage of the internal jugular vein approach to the central circulation may be an elevated intracranial pressure. The purpose of this prospective study was to evaluate the effect of right internal jugular vein cannulation on intracranial pressure in patients who are at risk of intracerebral hypertension. Eleven adult patients studied in the intensive care unit were evaluated. The population included those patients who were admitted to the neurosurgical intensive care unit requiring intracranial pressure monitoring and central venous access. With the intracranial pressure monitor in place, patients were put in supine and 30 degrees head-up positions while intracranial pressure was recorded. The Queckenstedt maneuver was performed on all patients. A central venous line was then placed in the right internal jugular vein, and intracranial pressure was recorded. The Queckenstedt maneuver was again performed in the study population, and intracranial pressure measurements were recorded for the right, left, and bilateral compression of the internal jugular vein. The results of the intracranial pressure measurements before and after placement of the central venous line were statistically analyzed using single-factor analysis of variance over time. The mean Glasgow coma and Apache II scores for the study groups were 8 +/- 4 and 15 +/- 6, respectively. There were no significant differences in heart rate; cerebral perfusion pressure; or systolic, mean, or diastolic pressures throughout the study period. There was no statistical difference found between the intracranial pressures at any time point throughout the study. Furthermore, no difference was found in percentage change from baseline intracranial pressure data throughout the study period. Our results suggest that cannulation of the right internal jugular vein is a safe approach to the central circulation in patients at risk of intracranial hypertension. A description of the possible accommodating mechanisms are outlined.

Effect of oral clonidine premedication on anesthetic requirement, hormonal response, hemodynamics, and recovery in coronary artery bypass graft surgery patients.

STUDY OBJECTIVE: To examine how premedication with clonidine affects opioid use, hemodynamic effects, hormonal responses, and recovery effects. DESIGN: Double blind, placebo-controlled study. SETTING: Operating room and surgical intensive care unit of a university medical center. PATIENTS: 54 patients undergoing elective coronary artery bypass graft (CABG) surgery. INTERVENTIONS: Patients received approximately 5 micrograms/kg of oral clonidine or a placebo together with 40 micrograms/kg lorazepam 90 minutes prior to titrated sufentanil induction of anesthesia. Thirty minutes prior to cardiopulmonary bypass, a second dose of either approximately 5 micrograms/kg clonidine or placebo was given as a slurry via a nasogastric tube. MEASUREMENTS AND MAIN RESULTS: Opioid use, hemodynamic effects, hormonal responses, and recovery effects were recorded. Values for ten hemodynamic variables were compiled on the evening prior to surgery, prior to induction, and during seven additional events and compared. Catecholamines and beta-endorphins were measured prior to induction, after intubation, and after sternotomy. The amount of sufentanil used for induction, maintenance, and total opioid were compared. The times to awakening and response to verbal commands were compared. The two groups exhibited similar patient demographics, cardiopulmonary bypass time, and duration of surgery. Patients receiving clonidine required significantly (p < 0.04) less sufentanil for induction (clonidine: 2.19 +/- 0.95 micrograms/kg vs. placebo: 2.93 +/- 1.07 micrograms/kg) and total amount of sufentanil (clonidine: 9.1 +/- 3.9 micrograms/kg vs. placebo: 11.7 +/- 4.6 micrograms/kg). Patients receiving clonidine required significantly (p < 0.01) less isoflurane (9.7 +/- 6.8 MAC min vs. 19.7 +/- 9.9 MAC min) to maintain heart rate (HR) and mean arterial pressure (MAP) to within 15% of baseline without significant differences in other vasoactive drugs. Catecholamine concentrations were significantly (p < 0.02) lower in patients receiving clonidine without any difference in beta-endorphin concentrations. Patients receiving clonidine had significantly (p < 0.02) lower HR, systolic arterial pressure, MAP, and systemic vascular resistance prior to induction than patients receiving placebo without differences in other hemodynamic variables. CONCLUSION: Clonidine decreases opioid use and lowers hormonal response while maintaining stable hemodynamics in patients undergoing CABG with sufentanil anesthesia.

A comparison of pentamorphone and fentanyl in balanced anaesthesia during general surgery.

The purpose of our randomized, double-blind study of 64 unpremedicated healthy patients undergoing surgical procedures with a duration of at least 60 min was to compare 0.75 micrograms.kg-1 and 1 microgram.kg-1 pentamorphone with 5 micrograms.kg-1 and 7.5 micrograms.kg-1 fentanyl to determine which dose of opioid would reduce the requirement for isoflurane supplementation needed to maintain haemodynamic stability. At 21 points during the procedure, the haemodynamic variables of heart rate and systolic, diastolic, and mean arterial pressures were recorded. The use of isoflurane was quantified; the number of patients requiring inhaled anaesthetic, concentration peaks, MAC minutes, and duration of isoflurane use were noted. The number of equal-volume supplemental opioid analgesic doses, postoperative analgesics, occurrence of postoperative nausea, emesis, and antiemetic doses were compared. The four groups exhibited similar patient demographics, total dose of muscle relaxants, types of surgical procedures, and duration of surgery or anaesthesia. Haemodynamic variables were stable with no difference among the four study groups. The patients given pentamorphone demonstrated both delayed requirement (P < 0.05) and shorter duration (P < 0.05) of isoflurane supplementation. Patients given either 5 micrograms.kg-1 or 7.5 micrograms.kg-1 fentanyl needed isoflurane supplementation within 12 +/- 16 min and 12 +/- 17 min from induction respectively; while patients given either 0.75 micrograms.kg-1 or 1 microgram.kg-1 pentamorphone did not require isoflurane supplementation for 37 +/- 10 min and 43 +/- 26 min respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative and postoperative effects of vancomycin administration in cardiac surgery patients: a prospective, double-blind, randomized trial.

OBJECTIVES: In response to an increased frequency of Staphylococcus epidermidis infections in postoperative cardiac surgery patients, antibiotic prophylaxis was changed to include both vancomycin and cefazolin pre- and intraoperatively. Subsequent to the addition of vancomycin prophylaxis, clinical impression and retrospective analysis supported a correlation between vancomycin administration and post-cardiopulmonary bypass norepinephrine use. DESIGN: A prospective, double-blind, randomized study. SETTING: Tertiary care center in a university hospital. PATIENTS: A total of 58 patients undergoing elective coronary artery bypass surgery under high-dose fentanyl anesthesia. INTERVENTIONS: Patients were randomized to receive cefazolin and either vancomycin or normal saline pre-, intra-, and postoperatively in a double-blinded protocol. MEASUREMENTS AND MAIN RESULTS: Hemodynamic profiles and doses of administered vasoactive agents were calculated and recorded for all patients for both intra- and postoperative time periods. Hypotension consistent with vasodilation was treated with a norepinephrine infusion. The rate and frequency of norepinephrine infusions were tabulated for both groups. Hemodynamic profiles that were obtained after the administration of the initial dose of vancomycin or normal saline and before the induction of general anesthesia and those profiles obtained after the induction of general anesthesia until the initiation of cardiopulmonary bypass showed no difference between groups and no evidence of vasodilation secondary to vancomycin administration. However, subsequent doses of vancomycin in the intra- and postoperative periods were associated with a significantly greater frequency of norepinephrine infusions to maintain normal hemodynamic indices. In the vancomycin group, 50% of patients received a norepinephrine infusion in the intra- and/or postoperative period as compared with 14% in the normal saline group (p < .01). Furthermore, the group of patients who received vancomycin and subsequently required a norepinephrine infusion had significantly lower mean systolic arterial pressure, mean arterial pressure, and systemic vascular resistance as compared with all other groups. There were no differences between groups in the use of vasopressors (other than norepinephrine) or fluid balance. CONCLUSIONS: The results show that a significantly greater number of patients who received vancomycin required a norepinephrine infusion and that, despite norepinephrine infusion therapy, systemic vascular resistance was not normalized in this group of patients. The study supports the conclusion that perioperative administration of vancomycin in cardiac surgery patients may result in hypotension requiring the use of a vasopressor in an attempt to normalize hemodynamic indices.

Evaluation of a new blood-conserving arterial line system for patients in intensive care units.

OBJECTIVE: To evaluate blood samples obtained from a new blood-conserving arterial line system for the presence of hemodilution or heparin contamination. DESIGN: Prospective, clinical trial. SETTING: A coronary intensive care unit in a tertiary-care teaching hospital. PATIENTS: Cardiovascular patients in whom invasive arterial blood pressure monitoring was indicated. INTERVENTIONS: Paired blood samples were obtained from a conventional arterial line system and a new blood-conserving arterial line system for the measurement of hematocrit and partial thromboplastin time, and compared to evaluate for the presence of either hemodilution or heparin contamination. MEASUREMENTS AND MAIN RESULTS: A Bland-Altman bias analysis of the variability between the two blood draw methods was performed. The analysis indicated that a) a randomly determined partial thromboplastin time obtained from the blood-conserving arterial line would lie between 3.32 and -5.11 of the partial thromboplastin time taken from the conventional arterial line value with 95% confidence; and b) a randomly determined hematocrit obtained from the blood-conserving arterial line would lie between 1.97 and -1.85 of the hematocrit taken from the conventional arterial line value with 95% confidence. CONCLUSIONS: We concluded that a) blood samples obtained with the blood-conserving arterial line demonstrate no evidence of hemodilution or heparin contamination; b) the blood-conserving arterial line provides blood samples without the need for an initial volume of blood to be discarded; c) the blood-conserving arterial line provides a means for blood conservation in the intensive care setting.

Defining the dose range for esmolol used in electroconvulsive therapy hemodynamic attenuation.

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting, beta-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressure induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized Latin-Square study involving two matched-pair trials (placebo versus esmolol given as a 500-micrograms/kg bolus followed by either 300 micrograms.kg-1.min-1 [high dose], 200 micrograms.kg-1.min-1 [medium dose], or 100 micrograms.kg-1.min-1 [low dose] infusion of esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures were 160). We administered a 1-min bolus of placebo (normal saline) or esmolol at the rate of 500 micrograms.kg-1.min-1 followed by either high-, medium-, or low-dose esmolol or placebo for an additional 3 min. We then induced anesthesia with methohexital (1 mg/kg) and succinylcholine (0.5 mg/kg) IV. Ninety seconds after the administration of succinylcholine, the electrical stimulus was applied to induce seizure. The infusion of placebo or esmolol was discontinued 3 min after the electrical stimulus. Significant decreases were found in mean heart rate from minute 3 until minute 7 and in the maximum heart rate. The mean of each patient's maximum heart rate after seizure changed from 147 +/- 18 bpm in placebo patients to 112 +/- 20 bpm in high-dose esmolol patients; to 121 +/- 23 bpm in medium-dose esmolol patients; and to 124 +/- 20 bpm in low-dose esmolol patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Radial artery cannulation: a comparison of 15.2- and 4.45-cm catheters.

Eighty-nine patients were studied prospectively to compare the incidence of postdecannulation arterial thrombosis and ischemic complications associated with percutaneous insertion of two different radial artery catheters. Patients scheduled for peripheral vascular surgery were randomized to receive a 15.2-cm (6 in, Argon Medical Corp.) or 4.45-cm (1.75 in, Arrow International, Inc.) 20-gauge, Teflon catheter. Extremity blood flow was evaluated prior to cannulation and again after decannulation with the modified Allen's test, pulse-volume plethysmography, and Doppler ultrasound. The incidence of postdecannulation radial artery occlusion for 15.2-cm catheters was significantly less than for 4.45-cm catheters (4 of 45 cases versus 11 of 44 cases, p = 0.05). No case of temporary or permanent ischemic injury occurred. Radial artery transfixion (16 of 45 cases versus 5 of 44 cases, p = 0.01) and hematoma formation (5 of 45 cases versus 0 of 44 cases, p = 0.02) occurred more frequently during insertion of 15.2-cm catheters than 4.45-cm catheters. The number of arterial punctures during catheter insertion and the duration of cannulation were similar for both groups. Of the 8 patients with positive modified Allen's test who underwent radial artery cannulation, one suffered arterial occlusion. Radial artery cannulation with a 15.2-cm catheter was associated with a lower incidence of postdecannulation radial artery thrombosis than cannulation with the 4.45-cm catheter. Radial artery cannulation with longer catheters (greater than 5.0 cm) appears to be a safe practice.

Postoperative course after sufentanil or fentanyl anesthesia for coronary artery surgery.

Postoperative hemodynamic effects were compared in 50 patients randomly selected to receive either sufentanil, 25 micrograms/kg, or fentanyl, 100 micrograms/kg, anesthesia for coronary artery bypass grafting. The two groups exhibited similar patient demographics; dose of premedicants and muscle relaxants; and use of inhalation agents. Values for 15 hemodynamic variables were recorded at baseline and at six postoperative times. The times to awakening, response to verbal commands, and extubation were also noted. Patients who received sufentanil had a more stable course, with higher cardiac outputs, lower systemic vascular resistances, and a lower incidence of hypertension. Postoperatively, the two groups had similar values for time to awakening, response to verbal commands, and extubation. Elimination half-lives differed significantly: 554 +/- 91 minutes (fentanyl) versus 277 +/- 60 minutes (sufentanil). Serum concentrations of both decreased linearly. The added advantages of postoperative hemodynamic stability could be important in the choice of anesthetic.

Lidocaine local anesthesia for arthroscopic knee surgery.

Forty-five patients were evaluated during knee arthroscopy performed using local anesthesia produced by lidocaine with epinephrine to determine the dose-response relationship for operative analgesia. Serum lidocaine concentrations were also measured. Patients were randomized prospectively to receive 20 mL of 0.5%, 1.0%, or 1.5% lidocaine with epinephrine intraarticularly. Intraoperative discomfort was measured by verbal response on an 11-point linear pain scale. Pain scores were significantly higher in patients receiving 0.5% lidocaine during the first 45 min of surgery (P = 0.03). After 45 min, pain scores continued to be higher in the 0.5% lidocaine group than in the 1.0% or 1.5% groups, but the differences were not statistically significant. Ninety-four percent of patients in the 1.5% lidocaine group were willing to repeat this anesthetic technique for surgery compared with 83% of those in the 1.0% lidocaine group and 75% of those in the 0.5% lidocaine group (P greater than 0.05). The duration of postoperative analgesia was similar in all groups. Serum lidocaine concentrations before and 15, 30, 60, and 120 min after instillation of lidocaine were highest in the 1.5% lidocaine group with a peak concentration of 278 ng/mL. No patient had symptoms of lidocaine toxicity. We recommend that lidocaine concentrations of 1.0% or 1.5% be used when 20 mL is instilled intraarticularly for knee arthroscopy based on patient comfort and absence of lidocaine toxicity.

Esmolol reduces autonomic hypersensitivity and length of seizures induced by electroconvulsive therapy.

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting beta 1-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized study, involving four match-pair trials (placebo versus esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures, 160). We administered a 4-min infusion of either placebo or esmolol at the rate of 500 micrograms.kg-1.min-1. We then induced anesthesia with methohexital and succinylcholine. After administration of electrical stimulation for ECT, the rate of infusion decreased to 300 micrograms.kg-1.min-1 for three additional minutes and was then discontinued. Statistically significant reductions in mean heart rate from minute 2 until minute 15 and in maximum heart rate (the mean of each patient's maximum heart rate after seizure changed from 152 +/- 23 to 115 +/- 24 beats/min) occurred in patients given esmolol. During and immediately after infusion, arterial blood pressure also decreased. Finally, the length of seizures decreased, as manifested clinically from 48 +/- 18 to 39 +/- 14 s and on electroencephalogram from 86 +/- 41 to 67 +/- 28 s. We conclude that esmolol effectively controls the hyperdynamic response to ECT and reduces the length of seizures. The significance of the latter to the overall effectiveness of ECT is not known.

A comparison of enflurane with alfentanil anaesthesia for gynaecological surgery.

Forty patients undergoing gynaecological surgery were randomly assigned to receive either alfentanil and thiopentone for induction of anaesthesia, followed by alfentanil-N2O/O2 (60%/40%) for maintenance of anaesthesia, or low-dose fentanyl and thiopentone, followed by enflurane-N2O/O2 (60%/40%). More patients given enflurane developed a tachycardia (P less than 0.03) and 20% decreases in systolic and diastolic blood pressure. Times to recovery were significantly shorter after alfentanil than after enflurane. Plasma concentrations of alfentanil during induction suggested that haemodynamic and catecholamine responses were either less than, or did not differ from, baseline levels when the plasma concentration of the drug exceeded 150 ng ml-1. At extubation and the beginning of spontaneous breathing, the plasma concentration was 278 +/- 129 ng ml-1. Values for pharmacokinetic parameters of alfentanil were as follows: clearance, 5.2 +/- 2.0 ml kg-1 min-1; volume of distribution, 0.63 +/- 0.20 1 kg-1; and elimination half-life, 96.9 +/- 52.5 min. Two patients who had extended surgery had significantly lower plasma clearance of alfentanil and increased half-life. The authors conclude that the alfentanil technique was preferable to maintenance with enflurane.

Does nifedipine enhance the cardiovascular depressive effects of bupivacaine?

Inadvertent intravenous administration of bupivacaine has been shown to cause cardiovascular collapse in patients. Patients undergoing peripheral vascular surgery have a high incidence of coronary artery disease and frequently receive calcium channel antagonists such as nifedipine for treatment of angina. In this study, the effects of an accidental intravenous injection of bupivacaine during regional anesthesia in patients taking nifedipine was simulated using dogs. The sling-trained dogs had baseline hemodynamic values recorded. Each dog was given a 10-mg sublingual loading dose of nifedipine in alcohol solvent followed by intravenous infusion of nifedipine at a rate of 5/micrograms/kg/min. After hemodynamic measurements were taken, increasing boluses of intravenous bupivacaine were administered until a 50% decrease in maximum left ventricle change in pressure with respect to time (LV dP/dt max) was observed. On the next day of the experiment, baseline hemodynamic measurements were recorded. The dog was given only the alcohol solvent portion of the nifedipine solution at a dosage and rate equivalent to that of the first day of the experiment. Next, increasing boluses of intravenous bupivacaine were administered exactly as on the first day until a 50% decrease in LV dP/dt max was observed. The results demonstrated that the total dose of bupivacaine given with nifedipine (8.7 +/- 3.7 mg/kg) to reach a 50% drop in LV dP/dt max was significantly less than the total dose of bupivacaine given without nifedipine (14.5 +/- 4.9 mg/kg); and the main effect of the combination of nifedipine and bupivacaine was to accentuate the decrease in LV dp/dt max caused by bupivacaine with the elimination of the compensatory increase in systemic vascular resistance to maintain blood pressure.

The PaCO2 rate of rise in anesthetized patients with airway obstruction.

Apneic, anesthetized patients frequently develop airway obstruction or may be disconnected from ventilatory support. The rate of PaCO2 rise is usually assumed to be equal to that of anesthetized humans who are receiving apneic oxygenation. Apneic oxygenation may eliminate CO2 because it requires a continuous O2 flow. The CO2 rate of rise in anesthetized humans with airway obstruction was measured. Fourteen consenting healthy adults were monitored continuously with pulse oximetry and EKG. Enflurane--O2 anesthesia was established for at least 10 minutes with normal PaCO2 without neuromuscular blockade so that anesthesia was deep enough to prevent spontaneous ventilation. Then, patients' tracheal tubes were clamped. Arterial blood samples were obtained before and after 0, 20, 40, 60, 120, 180, 240, and 300 seconds after clamping, provided that oxyhemoglobin saturation exceeded 0.92. The equation that best described the PaCO2 rise was a logarithmic function. Piecewise linear approximation yielded a PaCO2 increase of 12 mmHg during the first minute of apnea, and 3.4 mmHg/minute thereafter. These values should be employed when estimating the duration of apnea from PaCO2 change for anesthetized patients who lack ventilatory support. In addition, it appears that the flows of O2 that most earlier investigators used when delivering apneic oxygenation probably did not eliminate significant CO2 quantities.

The carbon dioxide rate of rise in awake apneic humans.

Currently available estimates of the PaCO2 rate of rise in resting humans with resting lung volume were gathered during general anesthesia. The PaCO2 rate of rise during apnea in awake subjects was determined to acquire a value that may be more applicable to awake, ventilator-dependent, critically ill patients. Clinically, apnea occurs at functional residual capacity. With FiO2 = 1.0, 20 volunteers held their breaths at functional residual capacity for 0, 10, and 20 seconds, and then for as long as possible. They exhaled through an infrared CO2 analyzer after each interval to determine end-tidal pCO2. An estimate of the logarithmic PaCO2 rise during breath holding at functional residual capacity was 7 mmHg during the first 10 seconds (43 mmHg/minute), 2 mmHg during the next 10 seconds (13 mmHg/minute), and 6 mmHg/minute thereafter. In conclusion, PaCO2 increases more rapidly in awake apneic humans than earlier thought. The values reported herein probably are better for estimating duration of apnea in conscious, critically ill patients than are values obtained during general anesthesia.

Effect of pleurotomy on pulmonary function after median sternotomy.

To determine whether pleurotomy during median sternotomy worsens postoperative pulmonary function, patients whose pleurae remained intact (N = 7) were compared with those whose pleural spaces were entered during median sternotomy (N = 31). Thirty-eight adults performed spirometry and N2 washout to determine functional residual capacity preoperatively and 2, 24, 48, and 72 hours after extubation. Two mediastinal drainage tubes were placed in every patient; no pleural drainage tubes were inserted. Chest roentgenograms were performed preoperatively and 24 and 72 hours after extubation. Preoperatively, functional residual capacity, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC did not differ between groups. Postoperatively, in all patients developed a restrictive pulmonary defect, but mean functional residual capacity, FVC, FEV1 and FEV1/FVC did not differ between groups. In contrast to earlier reports, entering the pleural space did not worsen the restrictive pulmonary defect that results from median sternotomy when direct pleural drainage was avoided.