Comparison of the effects of remifentanil andalfentanil on cardiovascular response to nasotracheal intubation: A prospective, randomized, double-blind study

Background:

Nasotracheal intubation is often necessary in patients undergoingelective or emergency maxillofacial surgery. Previous studies have suggested that the increase in blood pressure after nasotracheal intubation is significantly greater than the increase after orotracheal intubation. Many drugs, including narcotic analgesics, are effective in modifying cardiovascular responses to orotracheal intubation.

Objective:

The effects of remifentanil and alfentanil on the cardiovascularresponses to nasotracheal intubation were compared in healthy patients scheduled to undergo surgery.

Methods:

This prospective, randomized, double-blind study was conductedat the Department of Anesthesiology and Reanimation, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. Patients aged 16 to 65 years scheduled to undergo elective maxillofacial surgery and who were American Society of Anesthesiologists status I or 11 were randomly assigned to receive remifentanil 1 μg/kg in 10 mL saline over 30 seconds followed by an infusion of 0.5 μg/kg · min, or alfentanil 10 μg/kg in 10 mL saline over 30 seconds followed by an infusion of saline. Anesthesia was then induced with propofol, cisatracurium, and 1% isoflurane with 66% nitrous oxide in oxygen. Heart rate (HR) and systolic and diastolic arterial pressures (SAP and DAP, respectively) were measured noninvasively at 2 minutes before general anesthesia induction (baseline); 2 minutes after induction; and 1, 3, and 5 minutes after nasotracheal intubation. Patients were monitored for cardiac changes using electrocardiography.

Results:

Forty consecutive patients were enrolled in the study. Twenty patients (11 males, 9 females; mean [SD] age, 27.7 [12.6] years) received remifentanil, and 20 patients (12 males, 8 females; mean [SD] age, 31.5 [17.2] years) received alfentanil. Two minutes after anesthesia induction, mean (SD) arterial pressures decreased significantly from baseline in the remifentanil group (changes, 22 [8]/11 [6] mm Hg) and the alfentanil group (changes, 10 [9]/12 [8] mm Hg) (both, P < 0.05). Changes in SAP and DAP followed a similar pattern in both groups, but SAP was significantly lower in the remifentanil group compared with that in the alfentanil group throughout the study period (all, P < 0.05). After 1 minute of intubation, DAP was significantly lower in the remifentanil group compared with that in the alfentanil group (66 [9] mm Hg vs. 73 [20] mm Hg; P < 0.05). Compared with baseline, HR was decreased significantly in both groups throughout the study (all, P < 0.05). Except SAP in the alfentanil group, SAP, DAP, and HR were increased 1 minute after intubation compared with preintubation values. However, SAP, DAP, and HR remained significantly lower compared with baseline values throughout the study period in both groups (all, P < 0.05) except DAP at 1 minute after incubation in the alfentanil group. Five patients in the remifentanil group and 2 patients in the alfentanil group required treatment of hypotension. None of the patients in either group required treatment of bradycardia.

Conclusions:

In this study in healthy surgical patients aged 16 to 65 years, remifentanil 1 μg/kg given over 30 seconds, followed by a remifentanil infusion of 0.5 μg/kg · min, was similarly effective compared with alfentanil 10 μg/kg in attenuating the pressor response to nasotracheal intubation, but the incidence of hypotension in patients administered remifentanil was high.     

Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of mirodenafil: A single-dose,randomized-sequence,open-label,crossover study in healthy male volunteers in Korea

Background: Mirodenafil is a phosphodiesterase type 5 (PDE-5) inhibitor developed for the treatment of erectile dysfunction. Mirodenafil has the possibility of being administered with alcohol.Objective: This study assessed the hemodynamic effects and pharmacokinetic properties of mirodenafil administered with alcohol.Methods: This single-dose, randomized-sequence, open-label, crossover study was conducted in healthy male volunteers at the Clinical Trials Center, Seoul National University Hospital, Seoul, Korea. Volunteers were randomly allocated to 1 of 3 randomized-sequence groups, each of which consisted of 3 administration phases, each separated by a 1-week washout period: oral mirodenafil 100 mg, alcohol 0.5 g/kg, and both. Vital signs (systolic blood pressure [SBP], dia-stolic BP [DBP], and pulse rate) were measured before (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 hours after administration. Because volunteers were given a standardized meal at 4 hours after mirodenafil and/or alcohol administration, hemody-namic results were assessed using the maximum decrease from baseline during a period of up to 4 hours after administration. For pharmacokinetic assessment, serial blood samples were collected before (baseline) and at 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after administration. Tolerability was assessed using monitoring of adverse events (AEs), clinical laboratory parameters, and results of 12-lead electrocardiography.Results: A total of 20 subjects participated in the study (mean [range] age, 25.5 years [20–41 years]; weight, 69.8 kg [57.4–87.2 kg]; and height, 174.7 cm [168–186 cm]). Up to 4 hours after the administration of mirodenafil, alcohol, and mirodenafil + alcohol, the mean (SD) maximum decreases in SBP were 8.5 (3.5), 13.5 (7.8), and 15.1 (6.7) mm Hg, respectively, and the maximum decreases in DBP were 6.4 (4.8), 13.3 (7.4), and 13.8 (5.2) mm Hg. Simultaneous administration of mirodenafil + alcohol was associated with additional mean (95% CI) decreases in SBP and DBP of 1.7 mm Hg (?6.0 to 2.6 mm Hg) and 0.6 mm Hg (?4.7 to 3.6 mm Hg) compared with alcohol alone. Pharmacokinetic parameters of mirodenafil were not significantly different when the drug was administered with or without alcohol. The mean (SD) AUC_0?t values were 842.0 (434.7) ng/mL/h with mirodenafil and 833.4 (398.2) ng/mL/h with mirodenafil + alcohol. The most common AEs considered at least possibly related to study drug were nasal congestion (7 subjects [35%]), headache (3 [15%]), nausea (1 [5%]), and hiccups (1 [5%]).Conclusions: The concurrent administration of mirodenafil with alcohol was not associated with clinically significant hemodynamic changes in these healthy male volunteers in Korea. The pharmacoki-netics of mirodenafil were not significantly altered by this concurrent administration. Mirodenafil administered with alcohol had a tolerability profile comparable to that of mirodenafil alone.     

Comparison of the tolerability of recombinant human hyaluronidase + normal saline and recombinant human hyaluronidase + lactated ringer's solution administered subcutaneously: A phase IV, double-blind, randomized pilot study in healthy volunteers

Background: Recombinant human hyaluronidase (rHuPH20) (150 U) is approved by the US Food and Drug Administration to facilitate subcutaneous fluid administration in adults and children.Objective: This Phase IV, double-blind, randomized pilot study was designed to compare the tolerability, flow rate, and safety profile of subcutaneous infusions of normal saline (NS) and lactated Ringer's (LR) solutions following subcutaneous administration of rHuPH20.Methods: Healthy volunteers received 1 mL rHuPH20 (150 U) in each thigh, followed by simultaneous gravity-driven subcutaneous infusions of 500 mL of LR solution into 1 thigh and NS solution into the contralateral thigh. Subjects rated infusion-site discomfort in each thigh using a 100-mm (0 = no pain to 100 = most severe pain) visual analog scale (VAS) at baseline (ie, after catheter placement/ rHuPH20 injection and just prior to the start of the infusions) and at the following times: after infusion of 250 mL, after infusion of 500 mL (end of infusion), and when thigh circumference returned to within 5% of baseline. Adverse events (AEs) were recorded throughout the study. The primary tolerability end point was the maximal increase from baseline in infusion-site discomfort on the VAS. Secondary end points included infusion flow rate, change in thigh circumference, subject preference for leftversus right-thigh infusion, and safety profile measures.Results: Fifteen subjects (14 women, 1 man; mean age, 41 years [range, 20–60 years]) were included in the study. Mean (SD) maximal increase from baseline VAS pain score was significantly greater with NS solution than with LR solution (20.0 [19.4] vs 9.4 [18.3] mm, respectively; P = 0.005). Mean infusion flow rate was not significantly different between the NS and LR solutions (384.1 [118.1] vs 395.8 [132.8] mL/h). No significant differences between solutions were observed in mean maximal change in thigh circumference (5.2% [1.6%] vs 5.3% [1.5%]). All subjects expressed global preference for LR infusion over NS infusion. All subjects experienced ≥1 AE; the majority of AEs were mild, localized infusion-site reactions. Of all AEs (regardless of their relationship to study drug or procedure), 81% were mild injectionsite reactions that were similar in nature for the NS and LR solutions. Although the types of mild local AEs were similar for the 2 infusions, they were numerically more common with NS infusions (15 subjects [100%]) than with LR infusions (9 subjects [60%]). For the NS and LR solutions, the most frequent infusion-site AEs were pain (67% vs 40%, respectively), erythema (47% vs 13%), and irritation (27% vs 20%).Conclusions: This small pilot study found that the mean maximal increase from baseline in self-assessed pain VAS scores was statistically significantly higher with NS solution than LR solution. In addition, all subjects preferred LR solution to NS solution, and the incidence of some infusion-site AEs was numerically greater with NS solution. Although the VAS score indicated a statistically significant difference in tolerability favoring LR, the modest changes from baseline suggest both solutions were generally well tolerated and support the use of both NS and LR, as appropriate, for rHuPH20-facilitated subcutaneous isotonic fluid infusion in healthy adults. These results need to be confirmed in larger, controlled clinical studies.     

Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes and hemodynamic responses to tracheal extubation during rhinoplasty: A double-blind, randomized, controlled study

Background: Stimulation of various sites, from the nasal mucosa to the diaphragm, can evoke laryngospasm. To reduce airway reflexes, tracheal extubation should be performed while the patient is deeply anesthetized or with drugs that do not depress ventilation. However, tracheal extubation during rhinoplasty may be difficult because of the aspiration of blood and the possibility of laryngospasm. Dexmedetomidine and fentanyl both have sedative and analgesic effects, but dexmedetomidine has been reported to induce sedation without affecting respiratory status.Objective: The aim of this study was to compare the effects of dexmedetomidine and fentanyl on airway reflexes and hemodynamic responses to tracheal extubation in patients undergoing rhinoplasty.Methods: This double-blind, randomized, controlled study was conducted at the Erciyes University Medical Center, Kayseri, Turkey. Patients classified as American Society of Anesthesiologists physical status I or II who were undergoing elective rhinoplasty between January 2007 and June 2007 with general anesthesia were eligible for study entry. Using a sealed-envelope method, the patients were randomly divided into 2 groups (20 patients per group). Five minutes before extubation, patients received either dexmedetomidine 0.5 μg/kg in 100 mL of isotonic saline or fentanyl 1 μg/kg in 100 mL of isotonic saline intravenously. All patients were extubated by anesthesiologists who were blinded to the study drugs, and all were continuously monitored for 15 minutes after extubation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation using pulse oximetry (SpO₂) were recorded before anesthesia, after drug administration, after skin incision, at the completion of surgery, and 1, 5, and 10 minutes before and after tracheal extubation. Any prevalence of laryngospasm, bronchospasm, or desaturation was recorded.Results: Forty patients (25 men, 15 women; mean [SD] age, 24.86 [7.43] years) were included in the study. Dexmedetomidine was associated with a significant increase in extubation quality compared with fentanyl, reflected in the prevalence of cough after extubation (85% [17/20] vs 30% [6/20] of patients, respectively; P = 0.001). There were no clinically significant decreases in HR, SBP, DBP, or SpO₂ after extubation with dexmedetomidine or fentanyl. In the dexmedetomidine group, HR was not significantly increased after extubation; however, in the fentanyl group, HR was significantly increased compared with the preextubation values (all, P = 0.007). HR was significantly higher in the fentanyl group compared with the dexmedetomidine group at 1, 5, and 10 minutes after extubation (all, P = 0.003). Compared with preextubation values, SBP was significantly increased at 1 and 5 minutes after extubation in the dexmedetomidine group (both, P = 0.033) and at 1, 5, and 10 minutes after extubation in the fentanyl group (all, P = 0.033). The postoperative sedation scores and the extubation, awakening, and orientation times were not significantly different between the 2 groups. In the dexmedetomidine group, bradycardia (HR <45 beats/min) was observed in 2 patients and emesis was observed in 2 patients. In the fentanyl group, emesis was observed in 3 patients, bradycardia in 2 patients, vomiting in 1 patient, and shivering in 1 patient; vertigo was reported in 1 patient. There were no significant differences in the prevalence of adverse events between the 2 groups.Conclusion: The findings in the present study suggest that dexmedetomidine 0.5 μg/kg IV, administered before extubation, was more effective in attenuating airway reflex responses to tracheal extubation and maintaining hemodynamic stability without prolonging recovery compared with fentanyl 1 μg/kg IV in these patients undergoing rhinoplasty.