|Year : 2019 | Volume
| Issue : 1 | Page : 1-6
Ketamine versus in total intravenous anesthetic management of children undergoing strabismus surgery: a prospective randomized controlled study
Mohammed El-Saied Hamada, Thanaa M El-Nomani, Ghada F El-Baradey, Hesham El-Sayed El-Ashry
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||01-Jun-2017|
|Date of Acceptance||07-Sep-2017|
|Date of Web Publication||17-Sep-2019|
Mohammed El-Saied Hamada
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, El-Gharbia, Tanta, Mohammed Farid Street
Background Strabismus is a malalignment of the visual axes. Manipulation of the globe and traction on the extraocular muscle can elicit oculocardiac reflex (OCR). Propofol anesthesia is associated with rapid induction and recovery with minimal postoperative confusion, while ketamine anesthesia is associated with less hemodynamic changes. Thus both are preferred for anesthesia of strabismus surgery in pediatric patients.
Aim The aim of this work was to compare total intravenous anesthesia (TIVA) with ketamine versus propofol in the anesthetic management of children undergoing strabismus surgery.
Patients and methods This study had been carried out on 50 children with ASA I scheduled for strabismus surgery. Patients were randomized into two equal groups (25 patients in each group). Group K: received TIVA with ketamine; group P: TIVA with propofol. Heart rate and mean arterial pressure, incidence of OCR, number of patients who needed intravenous atropine, recovery time, postoperative nausea and vomiting (PONV), evaluation of postoperative pain and finally the satisfaction score of the surgeon were recorded.
Results Heart rate and the incidence of PONV showed a significant decrease in group P in comparison with group K. Incidence of OCR, the need for usage of atropine and the severity of postoperative pain in group P was higher in comparison with group K. There were no significant differences between the two groups regarding satisfaction score of the surgeon
Conclusion TIVA with ketamine showed significant decrease in postoperative pain and incidence of OCR owing to its hemodynamic stability in comparison with propofol, which showed more rapid onset of action with rapid recovery and decreased incidence of PONV.
Keywords: anesthesia, ketamine, oculocardiac reflex, propofol, strabismus
|How to cite this article:|
Hamada ME, El-Nomani TM, El-Baradey GF, El-Sayed El-Ashry H. Ketamine versus in total intravenous anesthetic management of children undergoing strabismus surgery: a prospective randomized controlled study. Tanta Med J 2019;47:1-6
|How to cite this URL:|
Hamada ME, El-Nomani TM, El-Baradey GF, El-Sayed El-Ashry H. Ketamine versus in total intravenous anesthetic management of children undergoing strabismus surgery: a prospective randomized controlled study. Tanta Med J [serial online] 2019 [cited 2020 Feb 27];47:1-6. Available from: http://www.tdj.eg.net/text.asp?2019/47/1/1/267020
| Introduction|| |
Strabismus is a malalignment of the visual axes. It is the most common cause of pediatric ophthalmic surgery ,.
The orbital structure includes six extraocular muscles (EOMs) which move the globe within the orbit are manipulated during surgery ,.
Manipulation of the globe and traction on EOM can elicit oculocardiac reflex (OCR). In general, OCR is defined as a decrease in heart rate (HR) of more than 20% from baseline HR after pressing globe ,.
A variety of methods such as premedication using atropine, normoxia, normocapnia, and adequate depth of anesthesia have been used to prevent the OCR. However, none of them has been found satisfactory .
Strabismus surgery may be also associated with significant postoperative pain  and postoperative nausea and vomiting (PONV) with an incidence of 20–30% .
Propofol and ketamine are sedative and hypnotic anesthetic agents ,, propofol has a pharmacokinetic action leading to rapid induction and recovery with minimal postoperative confusion ,, while ketamine anesthesia is associated with less hemodynamic changes thus both are preferred for anesthesia of strabismus surgery in pediatric patients .
| Aim|| |
The aim of this work was to compare total intravenous anesthesia (TIVA) with ketamine versus propofol in the anesthetic management of children undergoing strabismus surgery.
| Patients and methods|| |
This study had been carried out in the Ophthalmology Department of Tanta University Hospitals for 1 year on 50 children. A written informed consent had been obtained from children’s parents. Every patient’s parents have received explanation to the purpose of the study and patients had a secret code number to ensure privacy to participants and confidentiality of data. The study protocol and consent forms were approved by the Research Ethical Committee, Faculty of Medicine, Tanta University. The criteria for inclusion were children of either sex aged from 3 to 11 years, the ASA physical status 1 and scheduled for elective surgical repair of two EOMs. The criteria for exclusion are children with drug allergy, psychiatric disorders, or those whose families refused inclusion. Patients were randomly classified using a closed sealed envelope into two equal groups each of 25 patients according to the anesthetic drug used in induction and maintenance. Group K: patients received TIVA with ketamine. Group P: patients received TIVA with propofol.
Preoperative assessment: medical and surgical history of patients was evaluated, clinical examination was performed, all routine laboratory investigations were made including complete blood picture, and liver and kidney functions. On the arrival to operating room (OR), routine monitoring of HR and rhythm by ECG, arterial blood pressure using noninvasive blood pressure including systolic, diastolic and mean arterial blood pressure (MAP), peripheral oxygen saturation (SpO2) by using pulse oximeter and end tidal carbon dioxide (EtCO2) by using end tidal capnography was performed (using Nihon Kohden monitor; Nihon, Nitshiochial, Shinjuku-ku, Tokyo, Japan). Intravenous line was established with a 22 G cannula.
Ketamine was prepared in isotonic saline solution in a 50 ml syringe (1 cm=50 mg/50 ml saline) or propofol 1% was prepared (50 cm=500 mg in a 50 ml syringe) by assistant for intravenous infusion, after preoxygenation with 6 l/min O2, All patients received fentanyl 1 μg/kg, intravenous, then anesthesia induction by intravenous injection of either ketamine 1 mg/kg (in group K) or propofol 2 mg/kg (in group P) over 60 s; intubation was facilitated after giving intravenous cis-atracurium 0.15 mg/kg, the patients were left on controlled ventilation on 6 l/min of 100% oxygen. Anesthesia was maintained with intravenous infusion of ketamine at a rate of 1–3 mg/kg/h or propofol 1% at a rate of 6–9 mg/kg/h according to each group by using programmable syringe pump (Fresenius Kabi syringe pump). Additional bolus doses of both drugs had been given when needed signs of awareness appeared such as tachycardia, elevation of blood pressure, change in pupil size, lacrimation, and sweating). Before beginning of surgical traction of EOM by the surgeon and atropine was immediately available. All procedures were performed by the same surgeon.
At the end of surgery, intravenous anesthetic agents were discontinued; muscle relaxant was reversed using neostigmine 0.035 mg/kg given intravenously and atropine 0.01 mg/kg, intravenously; patients were extubated after regaining muscle power and protective reflexes.
Measurements: onset of action of each drug was calculated from the beginning of intravenous injection till reaching anesthetic depth that can be determined clinically by loss of verbal responsiveness. HR and MAP was recorded preinduction, postsurgical stimulation, 30 s before EOM manipulation, and immediately after manipulation (if the HR decreased from the basal HR by 20% beats/min, the surgeon was asked to release the EOM, if bradycardia did not improve; 0.01 mg/kg of atropine was given intravenously) and at the end of surgery. Incidence of OCR (defined as >20% decrease in HR from baseline values immediately after EOM manipulation) was recorded. The number of patients who needed intravenous atropine injection due to the reflex bradycardia during surgical manipulation of EOMs in each group was recorded. Recovery time was recorded as the time from the cessation of anesthetic agents to obtaining verbal communication using modified Aldrete score ([Table 1]) . PONV was evaluated via numeric rank score  (modified from Apfel by adding nausea) during the first hour postoperatively: 0=no nausea, 1=nausea, 2=vomiting once, 3=vomiting twice or more times. Evaluation of postoperative pain was performed using Faces Pain Scale (FPS) . The FPS criteria used in this study were adapted from the FPS in order to make it possible to score on the widely accepted 0–10 metric, Score the chosen face 0, 2, 4, 6, 8, or 10, counting left to right, so 0=no pain and 10=worst possible pain. At the end of the operation, the satisfaction score of the surgeon  was assessed according to the following numeric scale: 4=excellent (no complaint from the surgeon), 3=good (minor complaint without need for supplemental anesthetics), 2=moderate (due to the small motion of ocular globe back which required supplemental anesthetics), 1=unsuccessful (continuous ocular motion bothering the surgeon).
The sample size calculation is performed using EpI-Info (Atlanta, Georgia, US) 2002 software statistical package designed by WHO and by Centers for Disease Control and Prevention. The sample size is calculated as N more than 27 based on the following considerations: 95% confidence limit, 80% power of the study.
Statistical presentation and analysis was conducted by SPSS V.24 (SPSS Inc., Chicago, IL, USA). The results were expressed as mean±SD. Student’s paired t-test: for statistical analysis within the same group. Unpaired t-test: used for comparison of parametric data (age, weight, duration of surgery, onset of action, HR, MAP, recovery time) between the two studied groups. Modified χ2-test for small numbers: for comparison between two groups as regards qualitative data (sex). Mann–Whitney U-test: used for comparison of nonparametric data (satisfaction score). P value less than 0.05 was considered significant.
| Results|| |
Regarding the demographic data such as age, sex, weight, and the duration of surgery there was no significant difference between both groups (P>0.05). Duration of onset of action for group K patients was found to be significantly longer in comparison with group P (P<0.0001) ([Table 2]).
|Table 2 Demographic data, duration of surgery, onset of action, incidence of oculocardiac reflex, need for the usage of atropine, recovery time|
Click here to view
HR values ([Figure 1]) showed significant decrease (P<0.05) in group P in comparison with group K immediately after manipulation of EOM. Incidence of OCR in group P was significantly higher in comparison with group K (P<0.05).
|Figure 1 Comparison between both groups regarding heart rate (HR) (beat/min).|
Click here to view
The need for usage of atropine and the severity of postoperative pain in group P were statistically higher in comparison with group K (P<0.05).
Recovery time and the incidence of PONV in group K were found to be statistically higher in comparison with group P (P<0.05).
Regarding satisfaction score of the surgeon and MAP, there were no statistical significant differences between the studied groups.
| Discussion|| |
Strabismus surgery is performed to restore binocular single vision and for cosmetic reasons (extensively in childhood). There are some undesired effects of the surgery such as postoperative pain, anxiety, agitation, PONV, and OCR ,.
OCR carries risk of intraoperative cardiac dysrhythmias which prolongs the duration of surgery as temporary cessation of manipulation occurs each time OCR is elicited .
Propofol as an anesthetic agent with a pharmacokinetic profile leads to rapid induction and recovery times with minimal postoperative confusion and a smooth recovery without dysphoria along with its antiemetic and amnestic properties ,.
Ketamine is an anesthetic with both intrinsic analgesic and amnestic properties and protects airway reflexes. Ketamine activity has been suggested to be a result of the N-methyl-d-aspartate receptor antagonist property. Furthermore, small-dose ketamine increases thalamic sensory output and arousal ,.
As regards hemodynamic parameters, HR was statistically lower in group P in comparison with groups K following immediate manipulation of EOMs, which might be explained by the reduction of myocardial blood flow and myocardial oxygen consumption caused by propofol.
Mizrak et al.  have studied the effects of intravenous infusion of ketamine and propofol anesthesia in children undergoing strabismus surgery and they found that both HR and MAP; in group P the scores were significantly lower than in group K during intubation, incision, extubation, and after extubation periods.
Another study by Khutia et al.  compared intravenous infusion of propofol–ketamine (PK) as an alternative to intravenous infusion of propofol–fentanyl (PF) for deep sedation and analgesia in pediatric patients undergoing emergency short surgical procedures Their results showed that intraoperative MAP was significantly lower in group PF than group PK when compared with baseline values throughout the surgical procedure.
On the contrary, Nonaka et al.  concluded that TIVA with propofol and ketamine would be useful to stabilize hemodynamic state. Their results showed no statistical significance regarding HR and MAP. This might be explained by the different surgical procedure and age group studied, in addition to the sympathomimetic effect of ketamine administered during induction.
In the present study, regarding OCR, the results showed that the incidence of OCR in group K was statistically lower in comparison with group P (P<0.05) which might be attributed to the central sympathomimetic adrenergic effect of ketamine compared with the variable cardiodepressant effect of propofol.
In agreement, Mizrak et al.  concluded that the incidence of OCR in group K was significantly lower compared with group P.
Another study by Lee et al. , concluded that a single bolus of intravenous ketamine 1–2 mg/kg for anesthetic induction results in a lower incidence of OCR than propofol when combined with sevoflurane for maintenance in children undergoing strabismus surgery.
Choi et al.  have studied the effects of various anesthetic regimens on the incidence of OCR in pediatric strabismus surgery. They found that in patients given ketamine, OCR occurred more frequently in the ketamine–propofol (65.7%) group than in the ketamine–sevoflurane (37.1%) group. In patients given midazolam, OCR occurred more frequently in the midazolam–propofol (54.3%) group than in the midazolam–sevoflurane (31.4%) group. They concluded that propofol was associated with a higher incidence of OCR during pediatric strabismus surgery than sevoflurane, when either ketamine or midazolam was used as an induction agent.
Liu et al.  have investigated the advantages and disadvantages of sevoflurane-nitrous oxide (N2O) inhalation anesthesia and propofol–ketamine TIVA in children undergoing strabismus surgery. They found that the incidence of OCR was significantly lower in the volatile group than those in the TIVA group. This might be explained by the cardiodepressant effect of propofol added to ketamine compared with N2O with its tendency to stimulate the sympathetic nervous system by increasing endogenous catecholamine levels.
In the present study, the patients anesthetized with propofol seem to be more prone to develop pronounced OCR [15 (60%) patients] in comparison with [five (20%) patients] in the ketamine group. Three patients in the propofol group were administered atropine 0.01 mg/kg to treat persistent bradycardia. The OCR improved in 12 patients by releasing the traction first. Treatment with atropine (0.01 mg/kg) was only given in patients who had persistent OCR.
Tramer et al.  have shown that propofol, despite the use of anticholinergics, substantially increases the incidence of OCR. Propofol has the potency to increase the incidence of bradycardia by a central sympatholytic effect and vagal stimulation. Ketamine seems to protect against the parasympathetic activation induced by OCR.
Choi et al.  reported that 1–2 mg/kg of ketamine for anesthetic induction results in a lower incidence of OCR than propofol in children undergoing strabismus surgery.
In the present study, postoperative pain using faces pain scale was statistically higher in group P compared with group K (P<0.05).
In agreement with the results of the present study, Mizrak et al.  have found that postoperative pain using faces pain scale was statistically higher in the propofol group than in the ketamine group (P=0.001).
In the present study, the recovery time was evaluated by using modified Aldrete score and showed statistically longer recovery time in the ketamine group compared with the propofol group (P<0.0001). This most probably is related to ketamine metabolism and is due to an active metabolite norketamine with an elimination half-life of 2–3 h.
Erden et al.  studied the recovery time in children during extracorporeal shockwave lithotripsy following anesthesia. They found that significantly longer recovery time followed ketamine anesthesia than propofol–fentanyl.
Similarly, St Pierre et al.  investigated recovery from anesthesia with ketamine–propofol compared with alfentanil–propofol. They concluded that a TIVA with ketamine–propofol showed prolonged recovery compared with a TIVA with alfentanil–propofol.
In the present study, regarding PONV, results demonstrated that the incidence of PONV for patients in the ketamine group was statistically higher in comparison with the propofol group (P=0.0387).
Thorp et al.  reported that intravenous doses of ketamine-associated vomiting are not related to either the initial loading dose or the total dose, but the modest increase in receiving high cumulative doses.
Finally, there were no statistical significant differences among the studied groups regarding satisfaction score of the surgeon, where better satisfaction was achieved in group K (60%) than in group P (40%).
| Conclusion|| |
TIVA with ketamine showed significant decrease in postoperative pain and incidence of OCR owing to its hemodynamic stability in comparison with propofol, which showed a more rapid onset of action with rapid recovery and decreased incidence of PONV.
Being associated with the least incidence of OCR and better hemodynamic stability, we recommend the use of ketamine for both induction and maintenance of anesthesia during strabismus surgery in children.
However, further studies should be conducted to study the combination of either propofol with ketamine for anesthesia in strabismus surgery in children to gain more benefit with minimal side effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Feldman M, Patel A. Anesthesia for eye, ear, nose and throat surgery. Miller’s anesthesia. 7th ed. Philadelphia, PA; 2009. pp. 2380–2385.
McGoldrick KE. Anesthesia for ophthalmic and otolaryngologic surgery. WB Saunders Company; 1992.
Rodgers A, Cox RG. Anesthetic management for pediatric strabismus surgery: Continuing professional development. Can J Anaesth 2010; 57:602–617.
Dell R, Williams B. Anaesthesia for strabismus surgery: a regional survey. Br J Anaesth 1999; 82:761–763.
Mirakhur R, Jones CJ, Dundee J, Archer D. I.m. or i.v. atropine or glycopyrrolate for the prevention of oculocardiac reflex in children undergoing squint surgery. Br J Anaesth 1982; 54:1059–1063.
Zeltzer L, Kellerman J, Ellenberg L, Dash J, Rigler D. Psychologic effects of illness in adolescence. II. Impact of illness in adolescents − crucial issues and coping styles. J Pediatr 1980; 97:132–138.
Chhabra A, Pandey R, Khandelwal M, Subramaniam R, Gupta S. Anesthetic techniques and postoperative emesis in pediatric strabismus surgery. Reg Anesth Pain Med 2005; 30:43–47.
Wilhelm S, Standl T. Does propofol have advantages over isoflurane for sufentanil supplemented anesthesia in children for strabismus surgery? Anasthesiol Intensivmed Notfallmed Schmerzther 1996; 31:414–419.
Blanc V. Ventilation and the oculocardiac reflex. Anaesthesia 1987; 42:324–325.
Ohmi G, Hosohata J, Okada AA, Fujikado T, Tanahashi N, Uchida I. Strabismus surgery using the intraoperative adjustable suture method under anesthesia with propofol. Jpn J Ophthalmol 1999; 43:522–525.
Aldrete J, Kroulik D. A postanesthetic recovery score. Anesth Analg 1970; 49:924–934.
Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I et al.
A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004; 350:2441–2451.
Bieri D, Reeve RA, Champion GD, Addicoat L, Ziegler JB. The Faces Pain Scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties. Pain 1990; 41:139–150.
Mizrak A, Erbagci I, Arici T, Ozcan I, Ganidagli S, Tatar G et al.
Ketamine versus propofol for strabismus surgery in children. Clin Ophthalmol 2010; 4:673–679.
Lerman J, Eustis S, Smith D. Effect of droperidol pretreatment on postanesthetic vomiting in children undergoing strabismus surgery. Anesthesiology 1986; 65:322–325.
Janicki PK. Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonistsfor postoperative nausea and vomiting. Med Sci Monit 2005; 11:RA322–RA328.
Choi SR, Park SW, Lee JH, Lee SC, Chung CJ. Effect of different anesthetic agents on oculocardiac reflex in pediatric strabismus surgery. J Anesth 2009; 23:489–493.
Liu Y, Zeng Q. Sevoflurane-N2
O inhalation anaesthesia with laryngeal mask airway and propofol-ketamine intravenous anaesthesia in strabismus surgery. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2006; 31:97–99.
Khutia SK, Mandal MC, Das S, Basu S. Intravenous infusion of ketamine-propofol can be an alternative to intravenous infusion of fentanyl-propofol for deep sedation and analgesia in paediatric patients undergoing emergency short surgical procedures. Indian J Anaesth 2012; 56:145.
] [Full text]
Nonaka A, Suzuki S, Masamune T, Imamura M, Abe F. Anesthetic management by total intravenous anesthesia with propofol, pentazocine and ketamine. Masui 2005; 54:133–137.
Choi SH, Lee S, Kim S, Kim J, Kwon H, Shin Y, Lee KY. Single bolus of intravenous ketamine for anesthetic induction decreases oculocardiac reflex in children undergoing strabismus surgery. Acta Anaesthesiol Scand 2007; 51:759–762.
Tramer DM, Sansonetti A, Fuchs‐Buder T, Rifat K. Oculocardiac reflex and postoperative vomiting in paediatric strabismus surgery. A randomised controlled trial comparing four anaesthetic techniques. Acta Anaesthesiol Scand 1998; 42:117–123.
Erden A, Artukoglu F, Gozacan A, Ozgen S. Comparison of propofol/fentanyl and ketamine anesthesia in children during extracorporeal shockwave lithotripsy. Saudi Med J 2007; 28:364–368.
St Pierre M, Kessebohm K, Schmid M, Kundt H, Hering W. Recovery from anaesthesia and incidence and intensity of postoperative nausea and vomiting following a total intravenous anaesthesia (TIVA) with S-(+)-ketamine/propofol compared to alfentanil/propofol. Anaesthesist 2002; 51:973–979.
Thorp AW, Brown L, Green SM. Ketamine-associated vomiting: is it dose-related? Pediatr Emerg Care 2009; 25:15–18.
[Table 1], [Table 2]