| Protocol No: | ECCT/16/02/03 | Date of Protocol: | 05-11-2015 |
| Study Title: | EFFECT OF LOW-DOSE KETAMINE VERSUS FENTANYL ON ATTENUATING THE HAEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION IN PATIENTS UNDERGOING GENERAL ANAESTHESIA AT THE AGA KHAN UNIVERSITY HOSPITAL, NAIROBI |
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| Abstract of Study: | ABSTRACT Background The use of pharmacological agents to attenuate the haemodynamic response to laryngoscopy and endotracheal intubation is the standard of care for elective surgery in most institutions worldwide. Current evidence is conflicting concerning the best agent and optimal dose for this purpose. Fentanyl is widely utilized to attenuate haemodynamic compromise. Ketamine, a widely available drug, has been scarcely studied in this regard at low doses and against varying doses of other common agents. Objective The primary objective is to compare the overall incidence of hypertension and tachycardia immediately pre-intubation (post-induction) until 10 minutes post intubation between the study group receiving fentanyl at 1.0 mcg/kg and the group receiving Ketamine at 0.5 mg/kg. The secondary objectives are to compare the incidence of pre-laryngoscopy/intubation hypotension and of neuropsychiatric phenomena on emergence between the two groups. Primary outcome measure: Increase of SBP of more than 20% from the baseline. Study Setting: The Aga Khan University Hospital, Nairobi Study Design: A prospective, double blind, superiority, randomized control trial. Sample size: A sample size of 88 participants, 44 in each arm. Study population: ASA I and II patients aged 18-65 years scheduled for theatre for non-emergent surgery Anaesthetic Procedure: 88 adult patients will be randomly assigned to one of two groups corresponding to the agents applied for induction: (a) Fentanyl (1.0 µg/kg) added to Propofol (2.0 mg/kg) (F, n = 43) and (b) Ketamine (0.5 mg/kg) added to Propofol (2.0 mg/kg) (K, n = 43), and haemodynamic responses evaluated by determining heart rate and blood pressure immediately before laryngoscopy and at 2.5, 5, 7.5 and 10 min. This will be in addition to standard of care.
Data collection Data will be collected using a data collection tool (see appendix). Patients’ baseline characteristics, systolic blood pressure, mean arterial pressure, diastolic blood pressure and heart rate at baseline then at minute 1, 2.5, 5, 7.5 and 10 will be recorded. Data analysis Data analysis will be undertaken using the SPSS version 15 with the input of a statistician. All data and results will be tabulated. P < 0.05 will be considered statistically significant for all data. Demographic characteristics will be expressed as the following: Age (years), Weight (kg) and Height (cm) as mean ± SD; Sex (male/female) and ASA Class (I/II) as a ratio; Neuropsychiatric phenomena on recovery [n(%)] as a percentage. A minimum 20% change in the continuous variables (heart rate, SBP. MAP and DBP) relative to the baseline between the groups will be considered significant. These variables will be expressed as appropriate measures of central tendency i.e. means ± SD (or medians if not normally distributed) then analysed statistically with student's unpaired t-test (means) and chi-square test (proportions). For non-parametric data the Mann-Whitney-Wilcoxon test will be used. Compound line graphs will be used to present these results.* |
| 1 | Anaesthetic Procedure
108 adult patients were randomly assigned to one of two groups corresponding to the drugs used for induction: (a) Fentanyl (1.0 µg/kg) added to Propofol (2.0 mg/kg) and Cisatracurium (0.2 mg/kg) (F, n = 54) and (b) Ketamine (0.5 mg/kg) added to Propofol (2.0 mg/kg) and Cisatracurium (0.2 mg/kg) (K, n = 54), and haemodynamic responses evaluated by determining heart rate and blood pressure immediately before laryngoscopy and at 2.5, 5, 7.5 and 10 minutes. This was in addition to standard of care.
Results 108 ASA I and II patients scheduled to undergo elective surgery were included in this study, 54 participants (50%) in the Fentanyl arm and 54 (50%) in the Ketamine arm. Baseline demographic characteristics were similar between the groups. There were more hypertensive episodes in the Ketamine arm (11%) compared to the Fentanyl arm (1.85%), but not achieving statistical significance: Fisher’s exact test, p=0.06. There was no significant difference in the number of episodes of tachycardia between the Ketamine group 7/54 (13%) and the Fentanyl group, 6/54 (11%); x2=0.05, p=0.82. Hypotensive episodes were more common in those who received Fentanyl, 41/54 (76%), compared to Ketamine recipients, 21/54 (39%), X2=16.9, p<0.001. The use of Ketamine was associated with less episodes of hypotension, adjusted odds ratio = 0.18 (95% confidence interval 0.07, 0.45). According to the study protocol, various rescue actions and medications were to be employed in the case of persistent hypertension or tachycardia. This was not observed in any of the groups (no adverse events reported). There was no report of any patient with hallucinations or confusion deemed outside of the realm of post general anaesthesia behavior. Conclusion We conclude that there is no difference in the occurrence of hypertension with the use Ketamine at 0.5 mg/kg in combination with Propofol at 2.0 mg/kg. In this regard, Ketamine provides a viable alternative to Fentanyl at 1.0 mcg/kg for the purpose of attenuating the pressor response to laryngoscopy and endotracheal intubation. Additionally, our results suggest that Ketamine may protect against post-induction (pre-laryngoscopy) hypotension. |