Low-Dose Ketamine and Propofol Combination for Upper Endoscopy in Morbidly Obese Patients

Aim: The purpose of this randomized double-blinded study is to compare the safety and effi cacy of two different concentrations of ketofol on the intraoperative hemodynamics, respiration, bispectral index values and post-anesthesia recovery profi les in morbid obese patients undergoing upper GI endoscopy. Subjects and methods: Patients were randomly allocated into two groups, group I (k/p 1/2), no = 50, and group II (k/p 1/4), no = 50, after receiving ethics committee approval and informed patient’s consent. Patients in group I received bolus dose of ketamine 0.5 mg/kg + propofol 1 mg/kg, and group II received ketamine 0.25 mg/kg + propofol 1 mg/kg, intravenously in separate syringes (dosed ketamine then propofol). Incremental doses, half the fi rst dose of propofol (0.5 mg/kg) were given to get the desired depth of sedation, modifi ed by aiming at bispectral index (BIS) values between 70–80, and when the sedation was considered as inadequate by the endoscopist. The baseline measurements were obtained just before the administration of the study drugs. The primary outcome was emergence reactions (recovery agitation or hallucination) following the procedure. Results: There was no signifi cant difference between group I (k/p 1/2) and group II (k/p 1/4) as regard to demographic data (age, gender and BMI) and procedure duration. Discharge time from postanesthesia care unit (PACU) was prolonged in group I (Mean±SD = 38.34±4.28) compared to group II (Mean±SD = 33.11±4.89), p = 0.0001. The number of patients requiring propofol top-up doses was 20 (40%) in group I compared to 35 (70%) in group II (the low-dose ketamine group), p = 0.004. There was a signifi cant difference in the mean propofol top-up dose between the two groups (30±15 mg in group I and 41±13 mg in group II, p = 0.0002). No signifi cant difference between both groups as regard to BIS values and VAS pain score. Conclusion: The use of ketamine and propofol combination for upper GI endoscopy in morbid obese patients appears to be safe, effective and preserve the hemodynamic and respiratory parameters. Research Article Low-Dose Ketamine and Propofol Combination for Upper Endoscopy in Morbidly Obese Patients Hosni A Salem* Assistant Professor, Anesthesia and Intensive Care, Faculty of Medicine, Al-azhar University, Cairo, Egypt Dates: Received: 23 February, 2017; Accepted: 20 March, 2017; Published: 21 March, 2017 *Corresponding author: Hosni A Salem, Assistant Professor of Anesthesia and intensive care, Faculty of Medicine, Al-azhar University, Cairo, Egypt, Tel : 01001574386; Email:


Introduction
Procedural sedation and analgesia refers to the technique of administering sedatives or dissociative agents with or without analgesics to induce an altered state of consciousness that allows the patient to tolerate painful or unpleasant procedures while preserving cardiorespiratory Function [1]. The aim of PSA is mainly to provide sedation, anxiolysis, analgesia and thereby enhances patient cooperation throughout the procedure. It is important to keep in mind that, the level of sedation can easily and quickly passed from conscious to deep sedation and result in loss of protective refl exes and in problems related to airway control [2]. Agents reported to achieve PSA includes midazolam, ketamine, propofol, fentanyl, remifentanil and dexmedetomidine [3]. The use of ketamine and propofol for procedural sedation and analgesia external to the surgical environment has grown in popularity [4]. Sedative drug selection and the dose depend on the patient's emotional state, the intensity of pain during the examination, anticipated technical diffi culties, surgeon's experience and hospitalspecifi c policy and procedures. An ideal sedation regimen would provide patient comfort, cooperation, hemodynamic stability, amnesia and maintenance of a patent airway with spontaneous ventilation [5]. Propofol has become a preferred sedative because it offers advantages over benzodiazepines in terms of lack of accumulation, quick onset, easy adjustment, and fast recovery after discontinuation. It has sedative and hypnotic effects that mediate the GABA receptor but has no analgesic action. Adverse effects associated with propofol included pain on injection, hypotension, bradycardia, respiratory depression, and II, aged from 18 to 50 years with a Glasgow Coma Scale score 15. Patients were randomly allocated into two groups, group I (k/p1/2), no = 50, and group II (k/p1/4), no = 50, after receiving ethics committee approval and informed consent from patients. All procedures were performed by the same physician.

Exclusion criteria
ASA more than II, pregnant women, patients with drug abuse or had allergy to egg, hypersensitivity to ketamine or propofol, those who had severe bradycardia or any type of atrioventricular block, heart failure or refused to participate in the study.
In the operating room, patients were breathing spontaneously. Nasal oxygen (3 L/min) was administered and intravenous access was established. Standard monitoring All patients were premedicated with ondansetron 0.1 mg/kg, and glycopyrrolate 4 mcg/kg intravenously before induction.
Midazolam 0.02 mg/kg was given as premedication. Fentanyl 0.5 mcg/kg was given IV to patients in both groups before the start of endoscopy together with lidocaine local anesthetic spray and ointment. The upper GI endoscope was commenced after 30 seconds from injection of ketofol. Patients in the group I received bolus dose of ketamine 0.5 mg/kg + propofol 1 mg/ kg (k/p 1/2), and group II received ketamine 0.25 mg/kg + propofol 1 mg/kg (k/p 1/4) intravenously in separate syringes (separate syringe strategy). Incremental doses, half the initial dose of propofol (0.5 mg/kg) were given to get the desired depth of sedation, modifi ed by aiming at BIS values between 70-80 [17], and when the sedation was judged as inadequate by the endoscopist. A ketamine and propofol dose was prepared by an assistant who was not involved in the clinical management of the study patients.
The patients in the PACU were assessed with the fasttrack score. Total score of 14, with minimal score of 12 would be required, with no score below 1 in any individual category [18]. Each patient was informed about how to measure pain intensity on a VAS pain score subjectively using a VAS ruler 0-10, with 0 representing "no pain" and 10 "the worst pain" was assessed and any adverse events were recorded as pain, nausea, vomiting, shivering, emergence reactions (agitation or hallucination), visual disturbances, myoclonus, seizure, rash, any hypoxic episode or apnea (desaturation was defi ned as a 10% decrease in peripheral oxygen saturation when compared to baseline, and apnea was defi ned as cessation of respiration for 15 seconds or more.), any episodes of hypotension (decrease in MAP > 30% of baseline) or bradycardia (decrease in HR > 30% of the initial rate or HR < 55/min). Surgeons and patients were asked to grade their overall satisfaction with sedation technique using a 3 point scale [poor (1), fair (2), and good (3)]. The patients were discharged home with Aldrete's scores greater than 9 [19].

Statistical analysis
The collected data were statistically analyzed using SPSS version 16.0 (SPSS Inc., USA) for Windows (Microsoft Co, USA). Data were expressed as mean values ± SD or as number and percentages. Fisher's exact, Student's t and 2 tests were used for comparison of the quantitative and qualitative values of the two groups. P < 0.05 was considered statistically signifi cant.

Results
This randomized double-blinded study was conducted during a 10-month period in which 100 morbid obese patients had PSA with ketofol. All patients underwent their planned upper GI endoscopy and received their allocated study drug.
The general characteristics of studied cases and operative data were represented in Table 1. This Table shows that, there was no signifi cant difference between group I (k/p 1/2) and group II (k/p 1/4) as regard to demographic data (age, gender and BMI) and procedure duration. However, discharge time from PACU was prolonged in group I (Mean±SD = 38.34±4.28) compared to group II (Mean±SD = 33.11±4.89), p = 0.0001. The number of patients requiring propofol top-up doses was 20 (40%) in group I compared to 35 (70%) in group II (the low-dose ketamine group), p = 0.004. There was a signifi cant difference in the mean propofol top-up dose between the two groups (30±15 mg in group I and 41±13 mg in group II, p = 0.0002) as shown in Table 1. Heart rate increased after induction of sedation in both groups. The difference between the groups was statistically insignifi cant (p = 0.267). The change was least in group II (due to low ketamine dose), but no patient had severe tachycardia requiring treatment in both groups. There was a minimal decrease in MAP from baseline in both groups following the initial dose of ketofol. Heart rate and MAP decreased during procedure in group II compared to group I but this decrease is considered to be not quite statistically signifi cant (as p was 0.077 and 0.076 respectively). No signifi cant differences in SpO2 between the two groups (Table 2, Figure 1-3). No cases needed manual ventilation or artifi cial airway. Overall, cardiovascular and respiratory adverse events were not signifi cantly different between the two groups. These adverse events were transient and easily treated with no sequelae. There were no signifi cant differences between both groups as regard to BIS values and VAS pain score (Table 3). Table (4) shows that there is no signifi cant difference between the two groups regarding patient as well as surgeon satisfaction. Side effects are listed in (Table 5, Figure   4). The most common side effect was visual disturbances. No difference in the occurrence of PONV between the two groups.
Agitation on recovery, although not statistically signifi cant (p value = 0.111); was more commonly reported with group I   A two patients (4%) in group I and no patient (0%) in group II experienced bad dreams and hallucinations. Side effects such as myoclonus, seizure and rash were not observed in any patient.

Discussion
Our study compared the safety and effi cacy of two different Miner et al. [21], performed a randomized, double-blinded trial in which two hundred seventy-one adults in emergency      Coulter et al. [22], evaluated the ketofol in the different ratios for procedural sedation in the healthy pediatric patients.
They suggested that a 1:3 ratio of ketamine and propofol was the best combination for the intermittent dosing. Furthermore, the mixing ratio greater than 1:3 resulted in prolonged recovery.
Dal et al. [23], No serious adverse events were observed.
Ghadami et al. [24], compared the quality of sedation and side effects of two different ratios of ketofol in 60 pediatric patients under lumbar puncture or bone marrow aspiration.
The results confi rmed that the 1:3 ratio of ketofol had lower psychological side effects and shorter recovery time than the 1:2 ratio of ketofol. However, the quality of sedation, the total dose of drug, respiratory profi les and hemodynamic parameters were comparable in both groups. They observed that 1:3 ratio was better than 1:2, because it had a shorter recovery time, and total drug usage was reduced in this group. Incidence of hallucination and nausea were lower, although were not statistically signifi cant.
Wang et al. [25], Hashemi et al. [28], performed study using a mixture of the Willman and Andolfatto, [4] published a study of 114 patients requiring PSA mainly for orthopedic procedures were given a 1:1 mixture of propofol and ketamine and they concluded that "Ketofol procedural sedation and analgesia is effective and appears to be safe for painful procedures in the ED. Few adverse events occurred and were either self-limited or responded to minimal interventions. Patients and staff were highly satisfi ed and recoveries were rapid".
Akin et al. [30], published a trial on 60 patients between one month and 13 years of age undergoing cardiac catheterization who received sedation with propofol or propofol plus ketamine  Friedberg [35], in a prospective study of 1,264 patients undergoing procedural sedation and analgesia for surgical procedures with ketamine and propofol, concluded that this combination was safe and effective.