988 | Unwanted Intra-operative Penile Erection During Pediatric Hypospadiasis Repair Comparison of Propofol and Halothane Hamid Reza Abbasi,1 Seyed Soheil Ben Razavi,2 Mohammad Reza Hajiesmaeili,3 Shekoufeh Behdad,1 Mohammad Mehdi Ghiamat,4 Ahmad Eghbali5 Purpose: To compare the erectile effect of propofol and halothane on unwanted intra- operative penile erection (UIOPE) during pediatric hypospadiasis repair. Materials and Methods: One hundred and seventeen boys who were in the age range of 6 months to 6 years and referred for hypospadiasis repair to our referral teaching hospital were included in this randomized clinical trial. Patients were randomly assigned to one of the two study groups before anesthesia induction. Anesthesia was maintained with a continuous intravenous infusion of propofol and inhalational halothane in the propofol (P) and halothane (H) groups, respectively. Data regarding the patients’ age, weight, pre- and intra-operative chordee, UIOPE, anesthesia time, surgery time, hematoma formation, and wound infection were collected. The Chi-Square and Fisher’s exact tests were used for comparison. Results: No statistically significant differences were noted regarding age, weight, and pre- and intra-operative chordee between the two groups. The incidence of UIOPE (10.34% versus 57.63%; P = .000), anesthesia time (174.15 ± 15.02 versus 181.26 ± 15.19; P = .012), and surgery time (162.34 ± 12.99 versus 167.69 ± 13.90; P = .034) were signifi- cantly lower in group P compared with group H. Conclusion: The use of propofol during hypospadiasis surgical repair is more safe and effective than halothane in preventing UIOPE and reducing surgery and anesthesia time. Keywords: anesthesia, propofol, halothane, child, penile erection Corresponding Author: Mohammad Reza Hajiesmaeili, MD Department of Anesthesiology and Critical Care Medicine, Parsian Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Tel: 02164352326 Fax: 02164352326 E-mail: mr-hajiesmaeili@razi.tums.ac.ir 1Department of Anesthesiology, Shahid Sadoughi Hospital, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2Department of Pediatric Surgery, Shahid Sadoughi Hospital, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 3Department of Anesthesiology and Critical Care Medicine, Parsian Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4Department of Anesthesiology, Logh- man Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 5Department of Anesthesiology, Mofid Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran PEDIATRIC UROLOGY Pediatric Urology 989Vol. 10 | No. 3 | Summer 2013 |U R O LO G Y J O U R N A L INTRODUCTION Hypospadiasis repair is a relatively common pedi-atric urological procedure. In which, correction of the chordee is an important step.(1) If chordee is not diagnosed by history taking and physical exam in the pre-operative visit, drug-induced artificial erection or via saline injection into the corpora cavernosa is done at the beginning of surgical repair.(1) Thereafter, any erection dur- ing surgery is unwanted and very troublesome to perform the procedure.(2,3) Unwanted intra-operative penile erection (UIOPE) is mostly idiopathic; however, it may be caused by anesthesia.(2,3) Pe- nile engorgement can occur because of blood pooling and vascular resistance changes during general or neuroaxial an- esthesia.(4,5) Although the effects of anesthetic medications and methods have been widely studied on the female geni- talia, especially on the uterine blood flow, its specific effects on the male genitalia and UIOPE have not been completely discussed.(6) To the best of our knowledge, only two studies have reported penile erection during remifentanil anesthesia in children(7) and UIOPE and its management.(3) Due to different mecha- nisms of anesthetic drugs and methods, it seems that these drugs have different effects on UIOPE. General anesthe- sia with volatile or total intravenous anesthesia (TIVA) has been commonly used for hypospadiasis surgery. In our cur- rent clinical practice, we used propofol or halothane for the maintenance of pediatric anesthesia. This clinical trial was designed to compare the erectile effects of propofol and halo- thane during pediatric hypospadiasis repair. MATERIALS AND METHODS Patients and Study Design One hundred and seventeen boys in the age range of 6 months to 6 years, who had referred for surgical hypospadiasis repair and had American Society of Anesthesiologist (ASA) Physi- cal Status class I, were enrolled in this randomized clinical trial. Prior to the study, the approval of the university’s Ethics Committee and the institutional review board of the tertiary referral teaching hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, was obtained. Patients with airway abnormalities and adverse reactions to the study drugs were excluded. The study was designed as a randomized, investigator-blinded study. Only the anesthesi- ologist was aware of the study groups. All medications were administered by the attending pediatric anesthesiologist, who was familiar with the medications and the protocol. Anesthesia and Study Drugs From March 2006 to January 2009, all patients received a standardized anesthetic protocol with fentanyl 2 µg/kg IV and midazolam 0.05 mg/kg for premedication. After pre- oxygenation by face mask and O2 100%, anesthesia was induced with thiopental 4 mg/kg and atracurium 0.5 mg/kg. Tracheal intubation was performed after 3 minutes. The patients were randomly assigned to one of the two study groups using a sealed envelope technique before anesthesia induction. Anesthesia was maintained with a continuous in- travenous infusion of propofol 100 μg/kg/min and inhalation- al 0.5 to 1 MAC halothane in the propofol (P) and halothane (H) groups, respectively. Both groups received nitrous oxide (N2O) 50% + O2 50% during the maintenance of anesthesia. Intravenous ringer was the standard fluid management for intra-operative fluid maintenance and the replacement of flu- id deficits in patients with insufficient oral fluid intake. The following drugs were used in the study: thiopental (Sandoz GmbH, Kundl, Austria), propofol emulsion (Fresenius Kabi Austria GmbH, Austria), fentanyl, midazolam, and Atracu- rium (Glaxo Wellcome S.P.A Parma, Italy). Monitoring was done using standard anesthesia monitors. In the pre-operative visit, chordee was diagnosed by manual compression in the perineum and penile shaft. After the in- duction of anesthesia and before the beginning of anesthesia maintenance, classic artificial erection was induced by inject- ing saline into the corpora cavernosa. Unwanted intra-operative penile erection, which was defined as increase in size without hardness (grade 1 of the Erectile Hardness Grading Scale [EHGS]) during urethral reconstruc- tion was recorded by the surgeon (9). All surgical procedures were performed by an attending pediatric surgeon. Finally, halothane and propofol were discontinued and the effect of atracurium was reversed by the administration of neostig- mine 60 μg/kg and atropine 20 μg/kg. Data regarding the patients’ age, weight, pre- and intra-oper- Unwanted Intra-operative Penile Erection | Abbasi et al 990 | ative chordee, UIOPE, anesthesia time (time from induction of anesthesia to endotracheal extubation), surgery time (time from beginning of surgery to the end of bleeding control), hematoma formation, and wound infection were recorded by the pediatric surgeon. Statistical Analysis The sample size for each group was calculated to be 57 (pow- er = 90%, type 1 error = 5%, and significant difference = 25% for UIOPE). Chi-Square and Fisher’s exact tests were used to analyze data related to occurrence and frequency of pre- and intra-operative chordee and UIOPE during surgery in both groups. P values less than .05 were considered sta- tistically significant. Continuous data, including age, weight, anesthesia time, and surgery time were analyzed using inde- pendent sample Fisher’s exact t test, and expressed as mean ± standard deviation. All statistical analyses were done by SPSS software (the Statistical Package for the Social Sci- ences, Version 16.0, SPSS Inc, Chicago, Illinois, USA). RESULTS Of 117 patients, 58 (50.43%) were assigned to group P and 59 (49.57%) to group H. The patients’ characteristics (Ta- ble 1) and their intra- and postoperative data (Table 2) were compared. The patients’ characteristics and pre- and intra-op- erative chordee of both groups were well-matched. The type of hypospadiasis and kind of operation were similar in the studied groups (Table 1). Six patients in group P and 34 in group H had UIOPE dur- ing surgery (10.34% versus 57.63%, P = .000). Anesthesia (174.15 ± 15.02 versus 181.26 ± 15.19, P = .012) and surgery (162.34 ± 12.99 versus 167.69 ± 13.90, P = .034) times were significantly lower in group P compared with group H (Table 2). If the patients were divided in two groups according to the incidence of UIOPE, the differences between surgery and anesthesia times would be statistically significant (P = .000 and P = .000, respectively). The risk difference between the two groups and the number needed to treat (NNT) were 47.29% and 2.11, respectively. Hematoma formation and wound infection were not found in the patients of the two groups. DISCUSSION Unwanted intra-operative penile erection during penile sur- gery is a challenge for the surgeon. Penile engorgement and concurrent complications, such as excessive bleeding and surgical trauma leading to delayed surgery, complicate penile surgery.(2,3) We found that general anesthesia with propofol infusion may be more effective in decreasing the incidence of UIOPE, an- esthesia time, and surgery time during hypospadiasis repair as well as postoperative nausea and vomiting compared with halothane. Based on the NNT (2.11) and number needed to harm (0) in UIOPE, this study shows that the use of propofol during hypospadiasis surgical repair can be more safe than volatile anesthetics. Studies on the effects of halothane on the female genitalia, especially on the uterine blood flow, show that halothane can increase uterine blood flow and bleeding during surgi- cal procedures, such as cesarean section. Thus, it has been recommended to decrease halothane concentration after de- livery.(6) During anesthesia, the autonomic nervous system is depressed. Therefore, sympathetically-mediated vasocon- striction may subside and vascular engorgement may occur requiring deeper levels of anesthesia to prevent UIOPE. Volatile anesthetics increase uterine,(6) nasal sinuses,(4,5) and cerebral blood flows.(8) Penile blood flow is probably in- creased by changing penile vascular resistance with or with- out decreasing outflow drainage and increasing penile blood Pediatric Urology Table 1. Comparison of patients’ characteristics between the studied groups. Variables Group P (n = 58) Group H (n = 59) P Age (mean ± SD), mo Weight (mean ± SD), kg Pre-operative chordee, n (%) Intra-operative chordee, n (%) Type of hypospadiasis (Operation) Distal third (Mathieu) Glandular (MAGPI) Coronal (MAGPI) Mid shaft (Snod gross) Proximal type (Snod gross or TIP) Redo operation (Snod gross or TIP) 37.90 ± 21.78 18.85 ± 7.63 40 (68.97%) 41 (70.69%) 7 4 3 5 4 35 37.05 ± 21.88 18.09 ± 7.00 39 (66.10%) 42 (71.19%) 7 4 4 5 3 36 .834 .575 .740 .952 .973 .980 .714 .977 .680 .941 SD indicates standard deviation; MAGPI, meatal advancement with glandoplasty and increment; and TIP, transverse incised plate. 991Vol. 10 | No. 3 | Summer 2013 |U R O LO G Y J O U R N A L Unwanted Intra-operative Penile Erection | Abbasi et al volume; hence, penile engorgement and UIOPE could occur. In an anesthetized patient, effect of tactile stimulation could suppress, except in early stages and light anesthesia. Neu- roaxial and general anesthesia with volatile agent or TIVA may induce vasodilatation and pooling of blood in the venous sinuses of the penis. Therefore, penile engorgement during anesthesia is not uncommon.(2,3) Inhalational anesthetics, such as halothane, are widely used in pediatric patients. Various volatile anesthetics have differ- ent effects on the circulation of different organs. Their effects on the uterine,(6) cardiovascular,(9,10) nasal sinuses,(4,5) and brain(8) circulation have been studied. Halothane decreases vascular resistance in the uterus leading to increased uterine blood flow and blood volume.(6) The vasodilatation induced by anesthetics in the heart and brain is mediated by oxygen free radicals participation,(11) EDRF/cGMP-mediated vascular smooth muscle relaxa- tion,(12) potassium channel blockade,(10) and adenosine triphosphate–sensitive. The main methods to prevent UIOPE include use of deeper levels of anesthesia with a simultaneous induction of hypo- tension by sodium nitroprusside, dorsal nerve block paraly- sis, corporeal aspiration with or without shunting procedures, and ketamine, phenylephrine, epinephrine, amylnitrate, terb- utaline, noradrenaline, metaraminol, and epinephrine admin- istration.(13-15) Several studies have suggested that propofol reduces the in- cidence of postoperative nausea and vomiting and results in shorter emergence times.(15,16) Currently, propofol TIVA is more expensive than anesthesia with inhalational halothane and N2O. Considering the costs of treating postoperative nau- sea and vomiting and the costs of increased recovery room stay after inhalational anesthesia, TIVA could be cost-effec- tive.(16,17) Considering a reduction in anesthesia time, surgery time, complication of surgery, and probably, bleeding, use of propofol can cover its higher cost in comparison with inha- lational anesthesia. We did not observe any of the above-mentioned complica- tions during the surgery. However, this could be because of the small volume of bleeding. Therefore, this variable was not measured because. CONCLUSION According to our findings, the use of propofol during hy- pospadiasis surgical repair is more safe and effective than halothane in preventing UIOPE and reducing surgery and anesthesia time. However, further studies are suggested to compare the effects of other anesthetic drugs and methods to find the safest one. CONFLICT OF INTEREST None declared. ACKNOWLEDGEMENTS The authors would like to thank Z.H. 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