Ketamine-propofol sedation in circumcision

ABSTRACT

BACKGROUND AND OBJECTIVE:

To compare the therapeutic effects of ketamine alone or ketamine plus propofol on analgesia, sedation, recovery time, side effects in premedicated children with midazolam-ketamine-atropin who are prepared circumcision operation.

METHODS:

60 American Society of Anaesthesiologists physical status I-II children, aged between 3 and 9 years, undergoing circumcision operations under sedation were recruited according to a randomize and double-blind institutional review board-approved protocol. Patients were randomized into two groups via sealed envelope assignment. Both groups were administered a mixture of midazolam 0.05 mg/kg + ketamine 3 mg/kg + atropine 0.02 mg/kg intramuscularly in the presence of parents in the pre-operative holding area. Patients were induced with propofol-ketamine in Group I or ketamine alone in Group II.

RESULTS:

In the between-group comparisons, age, weight, initial systolic blood pressure, a difference in terms of the initial pulse rate was observed (p > 0.050). Initial diastolic blood pressure and subsequent serial measurements of 5, 10, 15, 20th min, systolic blood pressure, diastolic blood pressure and pulse rate in ketamine group were significantly higher (p < 0.050).

CONCLUSION:

Propofol-ketamine (Ketofol) provided better sedation quality and hemodynamy than ketamine alone in pediatric circumcision operations. We did not observe significant complications during sedation in these two groups. Therefore, ketofol appears to be an effective and safe sedation method for circumcision operation.

Keywords:
Ketamine-propofol; Sedation; Circumcision

RESUMO

JUSTIFICATIVA E OBJETIVO:

Comparar os efeitos terapêuticos da cetamina isolada ou combinação de cetamina-propofol em analgesia, sedação, tempo de recuperação e efeitos colaterais em crianças pré-medicadas com midazolam-cetamina-atropina programadas para procedimentos de circuncisão.

MÉTODOS:

60 crianças, estado físico ASA I-II (de acordo com a classificação da Sociedade Americana de Anestesiologistas), com idades entre três e nove anos, submetidas a procedimentos de circuncisão sob sedação, foram recrutadas de acordo com um protocolo de randomização duplo-cego aprovado pelo Conselho de Revisão Institucional. Os pacientes foram randomizados e alocados em dois grupos com o uso do método de envelopes lacrados. Ambos os grupos receberam uma mistura de midazolam 0,05 mg kg-1 + cetamina 3 mg kg-1 + atropina 0,02 mg kg-1 por via intramuscular, na presença dos pais na área de intervenções pré-operatórias. A indução foi realizada com propofol-cetamina no Grupo I ou cetamina isolada no Grupo II.

RESULTADOS:

Nas comparações entre os grupos foram observadas a idade, o peso, a pressão arterial sistólica inicial e a diferença em relação à taxa de pulso inicial (p > 0,050). A pressão arterial diastólica inicial e as mensurações seriadas subsequentes nos minutos 5, 10, 15 e 20 da pressão arterial sistólica, pressão arterial diastólica e taxa de pulso do grupo cetamina foram significativamente maiores (p < 0,050).

CONCLUSÃO:

Cetamina-propofol (cetofol) proporcionou melhor qualidade de sedação e estabilidade hemodinâmica que cetamina isolada em cirurgias pediátricas de circuncisão. Não foram observadas complicações significativas durante a sedação nos dois grupos. Portanto, cetofol parece ser um método de sedação eficaz e seguro para procedimentos de circuncisão.

Palavras-chave:
Cetamina-propofol; Sedação; Circuncisão

Introduction

Circumcision is a painful and stressful outpatient procedure in children.11. Choi WY, Irwin MG, Hui TW, et al. EMLA cream versus dorsal penile nerve block for postcircumcision analgesia in children. Anesth Analg. 2003;96:396-9. An ideal anesthetic agent for this operation should provide adequate analgesia, amnesia, sedation, immobility and short recovery time while should be avoid cardiovascular and respiratory depression, nausea-vomiting and agitation.

The combination of propofol and ketamine (ketofol) in the same syringe successfully produced adequate action for oncologic procedures,22. Aouad MT, Moussa AR, Dagher CM, et al. Addition of ketamine to propofol for initiation of procedural anesthesia in children reduces propofol consumption and preserves hemodynamic sta- bility. Acta Anaesthesiol Scand. 2008;52:561-5. interventional radiology,33. Aydin Erden I, Gulsun Pamuk A, Akinci SB, et al. Comparison of propofol-fentanyl with propofol-fentanyl-ketamine combina- tion in pediatric patients undergoing interventional radiology procedures. Pediatr Anesth. 2009;19:500-6. cardiac catheterization,44. Akin A, Esmaoglu A, Guler G, et al. Propofol and propofol-ketamine in pediatric patients undergoing cardiac catheterization. Pediatr Cardiol. 2005;26:553-7. hematological diseases55. da Silva PSL, de Aguiar VE, Waisberg DR, et al. Use of ketofol for procedural sedation and analgesia in children with hemato- logical diseases. Pediatr Int. 2011;53:62-7. in children. Opiods, midazolam, ketamine, propofol and dexmedetomidine are the generally preferred sedoanalgesic agents.66. Demiraran Y, Korkut E, Tamer A, et al. The comparison of dexmedetomidine and midazolam used for sedation of patients during upper endoscopy: a prospective, randomized study. Can J Gastroenterol. 2007;21:25-9. Propofol, as an intravenous anesthetic, is applied as an intermittent infusion for sedation in spinal anesthesia.77. Murphy PG, Myers DS, Davies MJ, et al. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth. 1992;68:613-8. If the long infusion duration is ignored, waking is provided at the time of terminating the infusion.88. Mikawa K, Akamatsu H, Nishina K, et al. Propofol inhibits human neutropil functions.. Anesth Analg 1998;87:695-700. Nonetheless, the use of propofol may cause cardiovascular and respiratory system depression.99. Ozkan-Seyhan T, Sungur MO, Senturk E, et al. BIS quided sedation with propofol during spinal anaesthesia: influence of anaesthetic level on sedation requirement.. Br J Anaesth 2006;6:645-9. Ketamine may be considered effective with direct sympathetic stimulation and norepinephrine by reuptake inhibition from the postganglionic sympathetic system.1010. Ikeda T, Kazama T, Sessler DI, et al. Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia.. Anesth Analg 2001;93:934-8. It also induces functional dissociation between the limbic and cortical system often referred to as 'dissociative anesthesia'. Protective airway reflexes are maintained during sedation and the high therapeutic index of ketamine makes this drug suitable for regional anesthesia.1111. Serour F, Cohen A, Mandelberg A, et al. Dorsal penile nerve block in children undergoing circumcision in a day-care surgery. Can J Anaesth. 1996;43:954-8.

Ketofol is prepared as a 1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL mixed in a 10 mL or 20 mL syringe and is constituted a solution which is 5 mg each of ketamine and propofol in each mililiters.

In this study we aimed to evaluate the effects of ketamine alone or ketamine plus propofol on analgesia, sedation, recovery time, and side effects in premedicated children with midazolam-ketamine-atropin who are undergoing circumcision operation.

Materials and methods

60 ASA physical status I-II children, aged between 3 and 9 years, undergoing circumcision operations under sedation were recruited according to a randomize and double-blind institutional review board-approved protocol. Patients with clinically significant neurological, respiratory, cardiovascular and psychiatric diseases were excluded from the study.

Patients were randomized into two groups via sealed envelope assignment. Both groups were administered a mixture of midazolam 0.05 mg/kg + ketamine 3 mg/kg + atropine 0.02 mg/kg intramuscularly in the presence of parents in the pre-operative holding area. After 5 min, children were included in the operating room. Monitoring for the procedure consisted of three lead ECG, SpO2 with plethysmography and noninvasive blood pressure. After placement of an intravenous cannula, patients were induced with propofol-ketamine in Group I or ketamine alone in Group II. Medication dosages, administration times, total procedure time, vital signs (non-invasive blood pressure, oxygen saturation via pulse oxymetry, heart rate, respiration rate), side effects, and sedation scores were recorded by the same anesthesiologist at the beginning of the procedure and after induction at 5 min and then every 5 min until the end of the procedure. The sedation levels of the patients were assessed by Ramsay sedation score; induction and maintenance were applied to target score of 2 or 3. Prilocaine was injected for the dorsal penile nevre block by the surgeon and the procedure was started. Through the circumcision procedure, when the drug doses were not sufficient to achieve the targeted sedation scores or when the patient moved, additional boluses of propofol-ketamine was administered in Group I or ketamine was administered in Group II. Supplemental drug requirements were noted. We also noted the adverse symptoms including desaturation (SpO2 < %90), apnea (>15 s), rash, agitation, vomiting, and increased secretions. All patients received oxygen supplementation via nasal cannula or by blow-by with a gas flow rate of 2 L/min throughout the procedure. All operations were performed by the same surgeon.

The Ramsay sedation scale used to determine the response to sedation and analgesia is graded as 5, deep sedation: 1, patient awake: 6, patient asleep with no response to any stimuli.

When the procedure was complete, the patients were transferred to the recovery room and their levels of sedation, discharge time, and adverse events were assessed at 5 min intervals. Discharge criteria were as follows: airway patent with adequate oxygenation; awake or easily aroused (minimal tactile or vocal stimulation might be necessary); swallowing reflex present, demonstrating ability to swallow clear liquids while protecting the airway; presedation level of responsiveness achieved.

Statistical analysis was made using Statistical Package for the Social Sciences15.0 (SPSS 15.0, SPSS Inc., Chicago, IL) software. All quantitative data were analyzed with the Kolmogorov-Smirnov test to show distribution. Data with normal distribution were expressed as mean ± standard deviation and data with non-normal distribution as median (inter quartile range). According to the distribution status of quantitative data independent sampling t-test or Mann-WhitneyU-test was used. The Chi-square test was used to compare categorical data. A confidence interval of 95% was defined and a value ofp < 0.05 was accepted as statistically significant.

Results

In the between-group comparisons, age, weight, initial systolic blood pressure, a difference in terms of the initial pulse rate was observed (p > 0.050). Initial diastolic blood pressure and subsequent serial measurements of 5, 10, 15, 20th min, systolic blood pressure ( Fig. 1), diastolic blood pressure ( Fig. 2) and pulse rate ( Fig. 3) in ketamine group were significantly higher (p < 0.050). Follow-up time in terms of the need for additional analgesic in ketofol group used significantly fewer analgesics (p < 0.050). Both groups were similar in terms of complications (p > 0.050).

Figure 1
Comparison of systolic blood pressure levels between groups.

Figure 2
Comparison of diastolic blood pressure levels between groups.

Figure 3
Comparison of heart rates between groups.

Discussion

According to American Society of Anaesthesiologists (ASA) data (2006), high doses of sedation have been reported to lead to respiratory depression and are an important reason for unexplained malpractice.1212. Bhananker SM, Posner KL, Cheney FW, et al. Injury and liabil- ity associated with monitored anesthesia care: a closed claims analysis. Anesthesiology. 2006;104:228-34. Anesthesia is a balance between the patient's state of wakefulness and the need for anesthetic medication. If an insufficient dose is administered, the patient's wakefulness increases while a high dose causes hemodynamic instability, prolonged time to waking and other complications.1313. Bruhn J, Myles PS, Sneyd R, et al. Depth of anaesthesia moni- toring: what's available, what's validated and what's next?. Br J Anaesth 2006;97:85-94. In relation to the response to sedation and analgesia, it was decided to use the Ramsay scale in the current study because it is easy to apply.1414. Hesselgard K, Larsson S, Romner B, et al. Validity and reliability of the Behavioural Observational Pain Scale for postoperative pain measurement in children 1-7 years of age. Pediatr Crit Care Med. 2007;8:102-8. 1515. Suraseranivongse S, Santawat U, Kraiprasit K, et al. Cross- validation of composite pain scale for preschool children within 24 hours of surgery.. Br J Anaesth 2001;87:400-5. and 1616. DeJonghe B, Cook D, AppereDeVecchi C, et al. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med. 2000;26:275-85. The ideal sedative agent for regional anesthesia should have a rapid onset of action, produce a level of sedation sufficient for patient comfort, and have a short duration of action.1010. Ikeda T, Kazama T, Sessler DI, et al. Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia.. Anesth Analg 2001;93:934-8. Generally, the intermittent intravenous application in sedation does not allow for the adjustment of the plasma concentration level of the medication and extends the time to waking.1717. Hohener D, Blumenthal S, Borgeat A. Sedation and regional I in the adult patient.. Br J Anaesth 2008;100:8-16.

A pharmacological disadvantage of propofol is its relatively narrow therapeutic range. Unlike opioids and benzodiazepines, an antagonist is not available to reverse the effects. Despite its high potential to induce respiratory depression and cardiovascular instability, propofol has been routinely administered by anesthesiologist.1818. Fredette ME, Lightdale JR. Endoscopic sedation in pediatric practice. Gastrointest Endosc Clin N Am. 2008;18: 739-51.

In this prospective, randomized study, we compared the safety and efficacy of ketamine/propofol combination (ketofol) and ketamine alone for circumcision operation under local anesthesia via penile block. Our study showed that ketofol supplied more effective and safety sedation than ketamine alone in children.

Circumcision is a painful operation and it usually is performed in children.1 Many studies are performed on the method of anesthesia in this operation and most of them involved penile block and caudal block with or without sedation/general anesthesia.1111. Serour F, Cohen A, Mandelberg A, et al. Dorsal penile nerve block in children undergoing circumcision in a day-care surgery. Can J Anaesth. 1996;43:954-8.

The clinical effects of propofol and ketamine are complementary. While propofol provides hypnosis, ketamine performs analgesia and stable hemodynamic activity,1919. Sakai T, Singh H, Mi WD, et al. The effect of ketamine on clin- ical endpoints of hypnosis and EEG variables during propofol infusion.. Acta Anaesthesiol Scand 1999;43:212-6. the combination of ketamine and propofol is renamed "ketofol" and is currently popular agent for procedural sedation.22. Aouad MT, Moussa AR, Dagher CM, et al. Addition of ketamine to propofol for initiation of procedural anesthesia in children reduces propofol consumption and preserves hemodynamic sta- bility. Acta Anaesthesiol Scand. 2008;52:561-5. 33. Aydin Erden I, Gulsun Pamuk A, Akinci SB, et al. Comparison of propofol-fentanyl with propofol-fentanyl-ketamine combina- tion in pediatric patients undergoing interventional radiology procedures. Pediatr Anesth. 2009;19:500-6. 44. Akin A, Esmaoglu A, Guler G, et al. Propofol and propofol-ketamine in pediatric patients undergoing cardiac catheterization. Pediatr Cardiol. 2005;26:553-7. and 55. da Silva PSL, de Aguiar VE, Waisberg DR, et al. Use of ketofol for procedural sedation and analgesia in children with hemato- logical diseases. Pediatr Int. 2011;53:62-7.

David and Shipp2020. David H, Shipp J. A randomized controlled trial of ketamine/ propofol versus propofol alone for emergency department pro- cedural sedation. Ann Emerg Med. 2011;57:435-41. compared the frequency of respiratory depression during emergency department procedural sedation with ketamine plus propofol versus propofol alone. Ketamine was applied only one as a 0.5 mg/kg via intravenous route at the beginning procedure, not was prepared ketofol. And they arrived at the conclusion of ketamine/propofol did not reduce the incidence of respiratory depression but resulted in greater provider satisfaction, less propofol administration and perhaps better sedation quality. In a study by Shah et al.,2121. Shah A, Mosdossy G, McLeod S, et al. A blinded, randomized controlled trial to evaluate ketamine/propofol versus ketamine alone for procedural sedation in children. Ann Emerg Med. 2011;57:425-33. which compared with ketamine alone and the combination of ketamine and propofol for pediatric orthopedic reductions, it was shown that ketamine/propofol combination produced slightly faster recoveries while also demonstrating less vomiting, higher satisfaction scores and similar efficacy and airway complications. Both groups did not experience significant respiratory depression and ketofol group had better sedation levels than ketamine group in our study. We found that ketofol provided more acceptable hemodynamy than ketamine alone. But we did not study for the sedation or recovery time.

In conclusion, ketofol provided better sedation quality and hemodynamy than ketamine alone in pediatric circumcision operations. We did not observe significant complications during in these two groups. Ketofol obtained by mixing ketamine with propofol provided appropriate analgesia and sedation.

Our results indicate that intravenously administered ketofol produces faster recovery time and safe sedation.

References

  • 1. Choi WY, Irwin MG, Hui TW, et al. EMLA cream versus dorsal penile nerve block for postcircumcision analgesia in children. Anesth Analg. 2003;96:396-9.
  • 2. Aouad MT, Moussa AR, Dagher CM, et al. Addition of ketamine to propofol for initiation of procedural anesthesia in children reduces propofol consumption and preserves hemodynamic sta- bility. Acta Anaesthesiol Scand. 2008;52:561-5.
  • 3. Aydin Erden I, Gulsun Pamuk A, Akinci SB, et al. Comparison of propofol-fentanyl with propofol-fentanyl-ketamine combina- tion in pediatric patients undergoing interventional radiology procedures. Pediatr Anesth. 2009;19:500-6.
  • 4. Akin A, Esmaoglu A, Guler G, et al. Propofol and propofol-ketamine in pediatric patients undergoing cardiac catheterization. Pediatr Cardiol. 2005;26:553-7.
  • 5. da Silva PSL, de Aguiar VE, Waisberg DR, et al. Use of ketofol for procedural sedation and analgesia in children with hemato- logical diseases. Pediatr Int. 2011;53:62-7.
  • 6. Demiraran Y, Korkut E, Tamer A, et al. The comparison of dexmedetomidine and midazolam used for sedation of patients during upper endoscopy: a prospective, randomized study. Can J Gastroenterol. 2007;21:25-9.
  • 7. Murphy PG, Myers DS, Davies MJ, et al. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth. 1992;68:613-8.
  • 8. Mikawa K, Akamatsu H, Nishina K, et al. Propofol inhibits human neutropil functions.. Anesth Analg 1998;87:695-700.
  • 9. Ozkan-Seyhan T, Sungur MO, Senturk E, et al. BIS quided sedation with propofol during spinal anaesthesia: influence of anaesthetic level on sedation requirement.. Br J Anaesth 2006;6:645-9.
  • 10. Ikeda T, Kazama T, Sessler DI, et al. Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia.. Anesth Analg 2001;93:934-8.
  • 11. Serour F, Cohen A, Mandelberg A, et al. Dorsal penile nerve block in children undergoing circumcision in a day-care surgery. Can J Anaesth. 1996;43:954-8.
  • 12. Bhananker SM, Posner KL, Cheney FW, et al. Injury and liabil- ity associated with monitored anesthesia care: a closed claims analysis. Anesthesiology. 2006;104:228-34.
  • 13. Bruhn J, Myles PS, Sneyd R, et al. Depth of anaesthesia moni- toring: what's available, what's validated and what's next?. Br J Anaesth 2006;97:85-94.
  • 14. Hesselgard K, Larsson S, Romner B, et al. Validity and reliability of the Behavioural Observational Pain Scale for postoperative pain measurement in children 1-7 years of age. Pediatr Crit Care Med. 2007;8:102-8.
  • 15. Suraseranivongse S, Santawat U, Kraiprasit K, et al. Cross- validation of composite pain scale for preschool children within 24 hours of surgery.. Br J Anaesth 2001;87:400-5.
  • 16. DeJonghe B, Cook D, AppereDeVecchi C, et al. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med. 2000;26:275-85.
  • 17. Hohener D, Blumenthal S, Borgeat A. Sedation and regional I in the adult patient.. Br J Anaesth 2008;100:8-16.
  • 18. Fredette ME, Lightdale JR. Endoscopic sedation in pediatric practice. Gastrointest Endosc Clin N Am. 2008;18: 739-51.
  • 19. Sakai T, Singh H, Mi WD, et al. The effect of ketamine on clin- ical endpoints of hypnosis and EEG variables during propofol infusion.. Acta Anaesthesiol Scand 1999;43:212-6.
  • 20. David H, Shipp J. A randomized controlled trial of ketamine/ propofol versus propofol alone for emergency department pro- cedural sedation. Ann Emerg Med. 2011;57:435-41.
  • 21. Shah A, Mosdossy G, McLeod S, et al. A blinded, randomized controlled trial to evaluate ketamine/propofol versus ketamine alone for procedural sedation in children. Ann Emerg Med. 2011;57:425-33.

Publication Dates

  • Publication in this collection
    Sep-Oct 2015

History

  • Received
    23 Jan 2014
  • Accepted
    10 Mar 2014
Sociedade Brasileira de Anestesiologia R. Professor Alfredo Gomes, 36, 22251-080 Botafogo RJ Brasil, Tel: +55 21 2537-8100, Fax: +55 21 2537-8188 - Campinas - SP - Brazil
E-mail: bjan@sbahq.org