Errol Lobo

Intravenous Remifentanil Placental Transfer, Maternal and Neonatal Effects

Background Remifentanil has not been studied in obstetric patients. This study evaluates the placental transfer of remifentanil and the neonatal effects when administered as an intravenous infusion. Methods Nineteen parturients underwent nonemergent cesarean section with epidural anesthesia and received 0.1 [micro sign]g [middle dot] kg‐1 [middle dot] min‐1 remifentanil intravenously, which was continued until skin closure. Maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood samples were obtained at delivery for analysis of drug concentrations of remifentanil, its metabolite, and blood gases. Maternal vital signs were monitored continuously, and pain and sedation levels were assessed intermittently. Apgar scores were obtained at 1, 5, 10, and 20 min, and Neonatal and Adaptive Capacity Scores were noted 30 and 60 min after delivery. Parturients and newborns were observed for at least 24 h after surgery for side effects. Results The means and SDs of UV:MA and UA:UV ratios for remifentanil were 0.88 +/‐ 0.78 and 0.29 +/‐ 0.07, respectively. Mean clearance was 93 ml [middle dot] min‐1 [middle dot] kg‐1. The mean UV:MA and UA:MV ratios for remifentanil acid were 0.56 +/‐ 0.29 and 1.23 +/‐ 0.89, respectively. The mean MA (remifentanil acid):MA (remifentanil) ratio was 2.92 +/‐ 3.65. There were no adverse effects on the neonates, but there was a sedative effect and respiratory depressant effect on the mothers. Conclusions Remifentanil crosses the placenta but appears to be rapidly metabolized, redistributed, or both. Maternal sedation and respiratory changes occur, but without adverse neonatal or maternal effects.

Modular branched stent graft for endovascular repair of aortic arch aneurysm and dissection

PURPOSE We describe a modular stent graft for use in endovascular repair of aneurysms of the aortic arch. METHOD Carotid-carotid and left carotid-subclavian bypass grafts are created surgically. Two large, fully stented grafts are inserted endoluminally. The proximal component is bifurcated, with a wide proximal trunk and two distal limbs, one long and narrow, the other short and wide. This component is inserted through the carotid artery and deployed with the trunk and short wide limb in the ascending thoracic aorta; the long narrow limb opens into the innominate artery. After delivery system removal and carotid artery repair, a distal component is inserted through a femoral approach to bridge the gap between the short, wide distal limb of the proximal component and the nondilated descending thoracic aorta. The result is a branched stent graft, implanted proximally into the ascending aorta and distally into the innominate artery and descending thoracic aorta. CONCLUSION The system has been used successfully to treat a large wide-necked pseudoaneurysm of the aortic arch.

Systemically Administered α2-Agonist-induced Peripheral Vasoconstriction in Humans

Background &agr;2-Adrenoceptors mediate both sympatholytic and vasoconstrictive hemodynamic effects. The goal of this study was to profile the peripheral vasoconstrictive effects of a selective &agr;2-adrenoceptor agonist in isolation from the sympatholytic effects it also induces. Methods The authors administered increasing plasma target concentrations of dexmedetomidine (0.075, 0.15, 0.3, and 0.6 ng/mL) or saline placebo to healthy young volunteers in whom the sympatholytic effects of the drug were attenuated in one of two ways: general anesthesia (propofol–alfentanil–nitrous oxide) or axillary brachial plexus block. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger (LTF) and hemodynamic variables. Measurements made before and during the four steps of infusion were compared by repeated-measures ANOVA. Results In anesthetized volunteers, all concentrations of dexmedetomidine increased LTF (vasoconstriction) and systolic blood pressure (P < 0.001 for both), whereas placebo did not. In awake volunteers, all concentrations decreased systolic blood pressure (P < 0.001). Concentrations of 0.15, 0.3, and 0.6 ng/mL decreased LTF (vasodilation) in the neurally intact hand; in contrast, the same concentrations increased LTF (vasoconstriction) in the sympathectomized hand (P < 0.001 for both). Conclusions The results of this study are the first to characterize the lower end of the dose–response curve for vasoconstriction induced by dexmedetomidine. By denervating the vascular bed of interest or by decreasing sympathetic nervous system activity, the authors were able to observe vasoconstriction induced by a systemically administered &agr;2-agonist with minimal interference from the sympatholytic effects of the drug.

Intraoperative clonidine administration to neurosurgical patients.

The goals of this two-part study were to determine the dose of clonidine to prevent postoperative shivering after mild hypothermia and to evaluate the effect of clonidine on recovery from anesthesia in patients undergoing surgery for intracranial lesions. We enrolled 48 patients undergoing elective supratentorial neurosurgical procedures into one of two studies. In study 1 (n = 14) we determined the ED50 of clonidine to prevent postoperative shivering after mild hypothermia (35°C) using Dixon’s up-and-down method. Clonidine dose for the first study patient was 3 &mgr;g/kg. The dose was then adjusted in 1-&mgr;g/kg increments for the following patients. Shivering was assessed for 1 h postoperatively. Study 2 (n = 34) was a prospective, randomized, double-blind, placebo controlled study to evaluate the effect of 3 &mgr;g/kg clonidine on recovery from anesthesia. At the beginning of dural closure, patients randomly received a 15-min infusion of either clonidine or normal saline. Recovery variables were studied for 2 h after the end of anesthesia. The ED50 of clonidine to prevent shivering was 1.1 ± 1.5 &mgr;g/kg in neurosurgical patients whose target core temperature was 35°C at the end of surgery. Compared with saline, 3 &mgr;g/kg of clonidine administered to neurosurgical patients 1 h before the end of anesthesia did not delay emergence from anesthesia nor did it have clinically significant sedative or hemodynamic effects. Our results imply that clonidine may be used in neurosurgical patients to prevent postoperative shivering after mild hypothermia.

Clonidine-induced vasoconstriction in awake volunteers.

UNLABELLED We evaluated the vasomotor effects of clonidine in awake subjects with an intact central cardiovascular regulatory system. To determine the lower limit of the vasoconstrictive effect of clonidine in awake volunteers, we blocked sympathetic innervation to the left arm by anesthetizing the brachial plexus. We then measured arterial blood pressure and vasoconstriction via finger volume plethysmography measuring infrared light transmitted through a fingertip (LTF). LTF values obtained from the left arm were compared with those from the neurally intact right arm during four progressively increasing IV doses of clonidine, targeting plasma clonidine concentrations of 0.3, 0.45, 0.68, and 1.0 ng/mL. Clonidine decreased systolic blood pressure (P < 0.004) from 135 +/- 8 mm Hg to 115 +/- 8 mm Hg and heart rate (P = 0.0017) from 68 +/- 7 mm Hg to 61 +/- 10 mm Hg. Clonidine decreased LTF by -12% +/- 11% (P < 0.0001) less than preinfusion values at the 0.68 ng/mL target concentration in the right hand. In contrast, in the left hand, clonidine increased LTF significantly more than (P < 0.0001) preinfusion values at all target concentrations, with a maximal increase of 30% +/- 7%. We conclude that IV clonidine, at doses that decrease arterial blood pressure, causes arterial vasoconstriction in awake subjects. IMPLICATIONS IV clonidine, at doses that decrease blood pressure, causes arterial vasoconstriction in awake subjects. These data suggest that an alpha-2 agonist with a high alpha-2a/alpha-2b selectivity should provide more profound sedative and analgesic effects with less undesirable vasoconstrictive effects.

Desflurane reduces the febrile response to administration of interleukin-2

Background Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane‐induced anesthesia produces a dose‐dependent inhibition of the febrile response. Methods Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/kg of interleukin‐2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm‐minus‐fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated‐measures analysis of variance and Scheffes F tests. Results Values are presented as mean +/‐ SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/‐ 2.0 [degree sign]C [center dot] h on the control day to 2.1 +/‐ 2.3 [degree sign]C [center dot] h during 0.6 MAC and to ‐1.4 +/‐ 3.1 [degree sign]C [center dot] h during 1.0 MAC desflurane‐induced anesthesia. Peak core temperature (elapsed time, 5–8 h) decreased in a dose‐dependent fashion: 38.6 +/‐ 0.5 [degree sign]C on the control day, 37.7 +/‐ 0.7 [degree sign]C during 0.6 MAC and 37.2 +/‐ 1.0 [degree sign]C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering. Conclusions Desflurane‐induced anesthesia produced a dose‐dependent decrease in integrated and peak core temperatures after administration of pyrogen, with 1.0 MAC essentially obliterating fever. Anesthetic‐induced inhibition of the pyrogenic response is therefore one reason that fever is an inconsistent clinical response to inflammation during surgery.

Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction

Objectives Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes. Methods We administered 1 μg/kg dexmedetomidine (an alpha-2 agonist) intravenously to 80 surgical patients in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF) and of hemodynamic variables. Results Dexmedetomidine increased LTF (vasoconstriction), induced an initial increase in systolic blood pressure and decreased heart rate in all genotype groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion, the increase in LTF was more pronounced (P=0.014) in the DD group compared to the DI and II groups. There were no significant differences in LTF values between the groups at the end of or 5 min after dexmedetomidine infusion. There were no differences in systolic blood pressure or heart rate values between the groups during or after the dexmedetomidine infusion. Conclusions The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.

Effect of α2B-Adrenoceptor Polymorphism on Peripheral Vasoconstriction in Healthy Volunteers

Background:Alpha-2B adrenoceptor is the vasoconstrictive subtype in the mouse. Human &agr;2B-AR deletion (D) allele has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction on &agr;2 activation. The goal of this study was to test the hypothesis that &agr;2B-adrenoceptor activation induces enhanced vasoconstriction in carriers of the DD genotype, compared with carriers of the insertion/insertion (II) genotype. Methods:The authors administered increasing doses of dexmedetomidine (targeting plasma concentrations of 0.15, 0.3, 0.6, and 1.2 ng/ml) to 16 healthy young volunteers (8 carrying the &agr;2B DD genotype, 8 carrying the II genotype) in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger, finger blood flow by venous occlusion plethysmography, and hemodynamic variables. Results:All concentration of dexmedetomidine increased light transmitted through the finger (vasoconstriction) and systolic blood pressure and decreased heart rate in both groups (P < 0.001 for all). Dexmedetomidine reduced finger arterial inflow only in the DD group (P < 0.001). Dexmedetomidine had no effect on finger venous outflow or venous capacitance. There were no significant differences between the II and DD groups in any of the variables. Conclusions:The results of this study confirm the &agr;2 agonist induced vasomotor and hemodynamic effects in peripheral vasculature. However, the results do not support the hypothesis that &agr;2B-adrenoceptor polymorphism has an effect on peripheral vasoconstriction in humans.

The effect of Pyrogen Administration on Sweating and Vasoconstriction Thresholds during Desflurane Anesthesia

BACKGROUND General anesthetics increase the sweating-to-vasoconstriction interthreshold range (temperatures not triggering thermoregulatory defenses), whereas fever is believed to only increase the setpoint (target core temperature). However, no data characterize thresholds (temperatures triggering thermoregulatory defenses) during combined anesthesia and fever. Most likely, the combination produces an expanded interthreshold range around an elevated setpoint. The authors therefore tested the hypothesis that thermoregulatory response thresholds during the combination of fever and anesthesia are simply the linear combination of the thresholds resulting from each intervention alone. METHODS The authors studied eight healthy male volunteers. Fever was induced on the appropriate days by intravenous injection of 30 IU/g human recombinant interleukin 2 (IL-2), followed 2 h later by an additional 70 IU/g. General anesthesia consisted of desflurane 0.6 minimum alveolar concentration (MAC). The volunteers were randomly assigned to the following groups: (1) control (no desflurane, no IL-2); (2) IL-2 alone; (3) desflurane alone; and (4) desflurane plus IL-2. During the fever plateau, volunteers were warmed until sweating was observed and then cooled to vasoconstriction. Sweating was evaluated from a ventilated capsule and vasoconstriction was quantified by volume plethysmography. The tympanic membrane temperatures triggering significant sweating and vasoconstriction identified the respective response thresholds. Data are presented as the mean +/- SD; P < 0.05 was considered significant. RESULTS The interthreshold range was near 0.40 degrees C on both the control day and during IL-2 administration alone. On the IL-2 alone day, however, the interthreshold range was shifted to higher temperatures. The interthreshold range increased significantly during desflurane anesthesia to 1.9+/-0.6 degrees C. The interthreshold range during the combination of desflurane and IL-2 was 1.2+/-0.6 degrees C, which was significantly greater than on the control and IL-2 alone days. However, it was also significantly less than during desflurane alone. CONCLUSION The combination of desflurane and IL-2 caused less thermoregulatory inhibition than would be expected based on the effects of either treatment alone. Fever-induced activation of the sympathetic nervous system may contribute by compensating for a fraction of the anesthetic-induced thermoregulatory impairment.

Ultrasound Guidance Reduces Percutaneous Nephrolithotomy Cost Compared to Fluoroscopy

OBJECTIVE To examine the cost factors associated with ultrasound and fluoroscopic guidance for percutaneous nephrolithotomy (PCNL) and to determine which method can be performed at a lower cost per case. METHODS A cost comparison study was performed utilizing clinical data from a prospectively maintained research database. We included the most recent 33 consecutive ultrasound-guided PCNL cases in 2016 and the most recent 40 consecutive fluoroscopy-guided PCNL cases before the operative surgeon transitioned to ultrasound guidance in May 2014. The total operative time and clinical outcomes were examined. Costs were extracted from the institution accounting systems and given a uniform multiplier to protect institutional financial reporting confidentiality. Comparisons were made using the Student t test and the chi-squared test. RESULTS After excluding outliers, 71 PCNL procedures were included in the analysis. Demographic data and stone characteristics were not different between ultrasound-guided and fluoroscopy-guided groups. However, the mean operative time for ultrasound-guided PCNL was significantly shorter (99.8 ± 27.0 vs 144.9 ± 55.1 minutes, P < .05). When capital equipment costs were included, the mean total cost per case of ultrasound-guided PCNL was approximately 30% less than fluoroscopy-guided PCNL (simulated costs with a uniform multiplier;