Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 2  |  Page : 160-165

Midazolam, ketamine, or fentanyl added to propofol as total intravenous anesthesia in skin grafting after burn in pediatrics: a comparative study


Lecturer of Anaesthesia, Department of Anaesthesia and Intensive Care, Menoufiya University, Menoufiya, Egypt

Date of Submission05-May-2014
Date of Acceptance15-Jul-2014
Date of Web Publication8-May-2015

Correspondence Address:
Hala M Koptan
Lecturer of Anaesthesia, Department of Anaesthesia and Intensive Care, Menoufiya University, Menoufiya
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.156664

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  Abstract 

Background
Total intravenous anesthesia is an alternative to inhalational anesthesia. The combination of two drugs to achieve hypnosis and analgesia is the most common regimen. The combination of propofol and other drugs (midazolam, ketamine, and fentanyl) can be used for induction and maintenance of anesthesia.
Aim of the study
This study aimed to compare the effects of propofol - midazolam, propofol - ketamine, and propofol - fentanyl on intraoperative hemodynamics, recovery, postoperative pain and sedation, and postoperative complications in skin grafting after burn in pediatrics.
Patients and methods
Ninety pediatric patients (4-11 years' old) scheduled for skin graft after burn (10-20%) were divided into three groups. In group I (the propofol - midazolam group), anesthesia was maintained by an infusion of propofol at a dose of 5 mg/kg/h plus midazolam infusion at a dose of 0.05 mg/kg/h. In group II (propofol - ketamine group), anesthesia was maintained by an infusion of propofol at a dose of 5 mg/kg/h plus ketamine infusion at a dose of 1.5 mg/kg/h. In group III (propofol - fentanyl group), anesthesia was maintained by an infusion of propofol at a dose of 5 mg/kg/h plus fentanyl infusion at a dose of 1 μg/kg/h.
Results
Propofol - ketamine was superior in intraoperative hemodynamic stability. The three groups were comparable in terms of recovery, orientation time, and postoperative complications. Pain and sedation scores were comparable between the three groups in the first postoperative hour, but in the second hour, the propofol - ketamine and the propofol - fentanyl groups showed a significant decrease compared with the propofol - midazolam group.
Conclusion
Propofol - ketamine showed more hemodynamic stability than the other two groups. The propofol - ketamine and propofol - fentanyl combinations prolonged analgesia and sedation more than propofol - midazolam.

Keywords: fentanyl, ketamine, midazolam, pediatrics, propofol, total intravenous anesthesia


How to cite this article:
Elham M, Feky E, Koptan HM. Midazolam, ketamine, or fentanyl added to propofol as total intravenous anesthesia in skin grafting after burn in pediatrics: a comparative study. Ain-Shams J Anaesthesiol 2015;8:160-5

How to cite this URL:
Elham M, Feky E, Koptan HM. Midazolam, ketamine, or fentanyl added to propofol as total intravenous anesthesia in skin grafting after burn in pediatrics: a comparative study. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Sep 15];8:160-5. Available from: http://www.asja.eg.net/text.asp?2015/8/2/160/156664


  Introduction Top


The depth of the burn in children is difficult to determine immediately and it may take time to determine the true depth. The burns may be superficial, of partial thickness, and of full thickness [1] .

The Lund - Browder chart is used to calculate the burned-body surface area in children and infants (the anterior and the posterior head constitute 8.5% each, the anterior and the posterior torso 18% each, the anterior and the posterior arm 4.5% each, each anterior and posterior leg 6.5%, and the genitalia constitute 1%) [2] .

Full-thickness burns are treated by a skin graft. A skin graft is used to cover the burn wound by transfer of healthy skin from one part of the body to a burned area. The surgeon cleans the burn wound by removing the dead tissue, takes a thin shaving of healthy skin and puts it on the clean burn wound, and the graft is fixed by staples or stitches; dressing is then put on the graft [3] .

Total intravenous anesthesia (TIVA) is a technique of general anesthesia that involves the use of intravenous drugs to anesthetize the patient without the use of inhalational agents [4] .

Propofol can be used as an induction anesthetic agent or as a part of the total intravenous infusion for the maintenance of anesthesia. Its action is mediated by potentiating GABAA receptor activity and also by acting as a sodium channel blocker [5],[6] .

Midazolam is a short-acting benzodiazepine and it acts by binding to the benzodiazepine site on GABAA receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening. It is used for sedation, induction, and maintenance of anesthesia [7],[8] .

Ketamine is an N-methyl-d-aspartate receptor antagonist and has also been found to bind to μ-opioid receptors type 2 and to s-receptors; ketamine interacts with muscarinic receptors, descending monoaminergic pain pathways, and voltage-gated calcium channels [9],[10],[11] .

Fentanyl binds μ-opioid agonists and it binds to G-protein-coupled receptors, which act as inhibitors of pain neurotransmitter by decreasing intracellular Ca2 + levels [12] .


  Aim of the study Top


This study aimed to compare the effects of propofol - midazolam, propofol - ketamine, and propofol - fentanyl on intraoperative hemodynamics, recovery, postoperative pain and sedation, and postoperative complications in skin grafting after burn in pediatrics.


  Patients and methods Top


This study was approved by the local Clinical Research Ethics Committee of Menoufiya hospital, and written informed consents were obtained from the parents of patients before surgery. Ninety patients with the American Society of Anesthesiologists (ASA) physical status I-II, age 4-11 years, scheduled for skin graft after burn (10-20%) were enrolled in a prospective study.

All patients were clinically examined and all routine investigations were performed.

Exclusion criteria included patients with cardiovascular diseases, psychiatric disorders, drug allergy and clotting disorders, or those whose families did not approve inclusion in the study.

In the operating room, standard monitors including pulse oximetry, ECG, mean arterial pressure (MAP) and end-tidal CO2 were used; the bispectral index (BSI) was also applied to all patients. Two 22-G cannulae were inserted into an available peripheral vein. Then the patients were divided randomly into three groups (30 patients each).

In the first group [the propofol plus midazolam group (PM)], patients received propofol (2 mg/kg) and midazolam at a dose of 0.05 mg/kg for induction of anesthesia; tracheal intubation was facilitated by 0.5 mg/kg of atracurium, and the anesthesia was maintained by an infusion of propofol at a dose of 5 mg/kg/h plus midazolam infusion at a dose of 0.05 mg/kg/h.

In the second group [the propofol plus ketamine group (PK)], patients received propofol (2 mg/kg) and ketamine at a dose of 0.5 mg/kg for induction of anesthesia; tracheal intubation was facilitated by 0.5 mg/kg of atracurium, and the anesthesia was maintained by an infusion of propofol at a dose of 5 mg/kg/h plus ketamine infusion at a dose of 1.5 mg/kg/h.

In the third group [the propofol plus fentanyl group (PF)], patients received propofol (2 mg/kg) and fentanyl at a dose of 1 μg/kg for induction of anesthesia; tracheal intubation was facilitated by 0.5 mg/kg of atracurium, and the anesthesia was maintained by an infusion of propofol at a dose of 5 mg/kg/h plus fentanyl infusion at a dose of 1 μg/kg/h.

The mean target was to maintain the BSI between 40 and 50, and if the BSI increased above 50, an additional dose of intravenous propofol (0.2 mg/kg) was administered as a bolus dose.

After completion of the surgery, patients were extubated when adequate spontaneous ventilation was established. Patients were transferred to the recovery room and then to the surgical ward.

The following parameters were assessed; intraoperative and postoperative MAP and heart rate (HR) at baseline and every 10 min until 10 min after extubation.

The number of patients who required an extra dose of propofol, the recovery time (the time from discontinuing anesthesia to extubation), and the orientation time [the time from cessation of anesthetics till the moment when the patient can answer two orientation questions (what is your name, where are you)] were recorded.

The postoperative pain score was assessed during awaking and every 30 min for 2 h using the faces pain-rating scale. The chosen faces score 0, 2, 4, 6, 8, or 10, counting left to right, so that 0 indicates no pain and 10 indicates too much pain [13] ([Figure 1]).
Figure 1: The Wong — Baker faces pain-rating scale.

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If the faces pain-rating scale was greater than 4, the patient was given a paracetamol injection of 0.15 mg/kg, and the number of patients requiring analgesia in the three groups was determined.

The Ramsay sedation score was recorded during awaking and every 30 min for 2 h postoperatively on a numerical scale: 1 = anxiety and completely awake, 2 = completely awake, 3 = awake but drowsy, 4 = asleep but responsive to verbal commands, 5 = asleep but responsive to tactile stimulus, and 6 = asleep and not responsive to any stimulus [14] .

The number of patients who required postoperative paracetamol was calculated in every group in the first 2 h. The incidence of postoperative complications - such as postoperative nausea and vomiting, postoperative respiratory depression (respiratory rate <10 breaths/min or peripheral arterial oxygen saturation <90%), and the use of antiemetic drugs - was also recoded.

Statistical data analysis

Data obtained from previous studies showed that the propofol - ketamine combination caused a high pulse rate and high arterial blood pressure compared with the propofol - fentanyl combination. According to this hypothesis, 90 patients were adequate for this study. Statistical analysis of data was carried out as for all comparisons; P value less than 0.05 was considered significant. The Minitab version 1.6 program was used in the statistical analysis (Pennsylvania, USA). The analysis of variance test was used for numerical values with data expressed as mean and SD, and the χ2 -test was used for categorical values with data expressed as the number of patients or the ratio. The Kruskal - Wallis test was used for postoperative pain and sedation scores, with data expressed as the median and interquartile range.


  Results Top


[Table 1] shows the demographic data; the three groups were comparable.
Table 1 Demographic data

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[Figure 2] shows the intraoperative HR; the PK group showed a significant increase in the HR compared with the other two groups after baseline. The PM and the PF groups were comparable in the HR changes.
Figure 2: Heart rate (HR). PF, propofol — fentanyl; PK, propofol — ketamine; PM, propofol — midazolam.*Statistically significant.

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[Figure 3] shows the intraoperative MAP; the PK group showed a significant increase in the MAP after baseline, compared with the other two groups. The PM and the PF groups were comparable.
Figure 3: Mean arterial blood pressure (MAP). PF, propofol — fentanyl; PK, propofol — ketamine; PM, propofol — midazolam.*Statistically significant.

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[Table 2] shows that the number of patients who required extra propofol dose in the PM group was significantly higher in comparison with the other two groups. The recovery and the orientation times were comparable between the studied groups.
Table 2 The number of patients who used extra propofol and recovery and orientation times

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[Table 3] shows the pain score after awaking and for 2 h thereafter. The PK and the PF groups showed a significant decrease in the pain score in the second hour compared with the PM group (prolonged postoperative analgesia).
Table 3 Pain scores

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[Table 4] shows the sedation score after awaking and for 2 h thereafter. The PK and the PF groups showed a significant increase in the sedation score in the second hour compared with the PM group (prolonged postoperative sedation).
Table 4 Ramsay sedation scores

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[Table 5] shows the postoperative complications: the number of patients requiring analgesia was higher in the PM group, whereas respiratory depression and postoperative nausea and vomiting were comparable between the three groups.
Table 5 Postoperative complications

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  Discussion Top


There are many advantages of TIVA as it leads to less pain, less nausea and vomiting, rapid recovery, decreased use of reversal agents, fewer morbid events, greater patient satisfaction, and faster hospital discharge [15] .

The current study is the first study that compares the combination of propofol with midazolam, ketamine, or fentanyl in skin grafting after burn in pediatric patients.

In the present study, the results of demographic data were comparable between the studied groups.

Regarding the hemodynamic variables (MAP and HR), they were significantly increased in the PK group in comparison with the PM and the PF groups.

These results were supported by the study conducted by Srivastava et al. [16] , who compared the addition of ketamine, midazolam, propofol, or saline to propofol as a coinduction in elective orthopedic or gynecological operations, and concluded that ketamine had the additional advantage of better hemodynamic stability.

In the study conducted by Tosun et al. [17] , who compared the addition of propofol and ketamine (PK) with propofol and fentanyl (PF) in pediatric patients who underwent upper gastrointestinal endoscopy, they concluded that the PK combination resulted in stable hemodynamics.

In the study conducted by Khutia et al., who compared the infusion of both propofol and ketamine with propofol and fentanyl in pediatric patients undergoing emergency short surgical procedures, they found that HR and MAP were significantly decreased in the fentanyl group [18] .

However, in the study conducted by Tosun et al. [19] , who compared the addition of propofol and ketamine (PK) with propofol and fentanyl (PF) in pediatric patients who underwent burn dressing, they demonstrated that the HR and MAP were comparable in both groups. This difference may be because the induction dose of propofol, ketamine, and fentanyl were different from the doses used in the current study.

Regarding the total dose of propofol and the recovery and the orientation times, the three groups were comparable.

In the study conducted by Butt and Ahmed [20] , who calculated the propofol dose during induction with the addition of ketamine or midazolam, they found that the two groups were comparable.

In the study conducted by Mahajan et al. [21] , who compared the addition of ketamine or fentanyl to propofol as TIVA, they concluded that the time of spontaneous eye opening was comparable between the two groups, and also the postoperative 30-min questionnaire was good in both groups.

In view of the postoperative pain score and the sedation score, the three groups were comparable in the first hour, but in the second hour, the PK and the PF groups showed a significant decrease in the pain score and an increase in the sedation score in comparison with the PM group (prolonged analgesia and sedation).

These results were concomitant with the study conducted by Dehkordi et al. [22] , who compared the effects of midazolam - propofol with fentanyl - propofol in microlaryngeal surgeries, and concluded that the midazolam group showed early consciousness.

Also, in the study conducted by Tosun et al. [17] , who compared the addition of propofol and ketamine (PK) with propofol and fentanyl (PF) in pediatric patients undergoing upper gastrointestinal endoscopy, they concluded that both groups were effective in sedation.

Also, in another study conducted by Tosun et al. [19] , who compared the addition of propofol and ketamine (PK) with propofol and fentanyl (PF) in pediatric patients undergoing burn dressing, they demonstrated that both propofol - ketamine and propofol - fentanyl combinations provided effective sedation and analgesia during dressing in pediatric burn patients.

Regarding the number of patients who required postoperative analgesia, it was significantly higher in the PM group in comparison with the other two groups. These results can be explained by the powerful analgesia of fentanyl and ketamine when compared with midazolam.

Regarding postoperative complications, the three groups were comparable. These results can be explained by the antiemetic effects of propofol.

This result is concomitant with the study conducted by Vallejo et al. [23] , who compared the effects of propofol - ketamine with propofol - fentanyl in outpatient laparoscopy, and concluded that there was a nonsignificant difference between the two groups.


  Conclusion Top


Propofol - ketamine showed more hemodynamic stability than the other two groups. The propofol - ketamine and the propofol - fentanyl combinations prolonged analgesia and sedation more compared with propofol - midazolam.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

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Morton NS. Total intravenous anaesthesia (TIVA) in pediatrics: advantages and disadvantages. Pediatr Anaesth 1998; 8:180-194.  Back to cited text no. 15
    
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Srivastava U, Sharma N, Kumar A, Saxena S. Small dose propofol or ketamine as an alternative to midazolam co-induction to midazolam. Indian J Anaesth 2006; 50:112-114.  Back to cited text no. 16
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Mahajan R, Swarnkar N, Ghash A. Comparison of ketamine and fentanyl with propofol in total intravenous anaesthesia: a double randomized clinical trial. Internet J Anesth 2009; 23:239-243.  Back to cited text no. 21
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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