Circulatory responses to propofol-ketamine combination compared to propofol alone for sedation during spinal anesthesia.
Abstract: The present study was undertaken to establish the efficacy of low dose propofol-ketamine infusion in maintaining hemodynamic stability when used for sedation as compared to propofol alone during spinal anesthesia. Sixty adult patients of either sex, belonging to ASA physical status I and II undergoing urological procedures were studied in a randomized manner. After administering spinal anesthesia with 0.5% bupivacaine, patients were assigned to two groups of 30 patients each. Group I (propofol-ketamine combination) received intial loading dose of propofol and ketamine followed by a continuous infusion of low dose propofol and ketamine whereas group II (propofol alone) received a bolus dose of propofol followed by a continuous infusion of propofol only. Hemodynamic parameters like heart rate, systolic blood pressure, diastolic blood pressure and sedation scores rated on a five point scale were recorded at baseline and at the predetermined intervals of 5, 10, 15, 20, 25, 30, 45, 60, 75 and 90 minutes after spinal anesthesia. It was found that heart rate, systolic and diastolic blood pressure was significantly higher in group I patients at various intervals as compared to group II patients, however sedation scores revealed no significant difference at different time intervals between the two groups. In conclusion propofol-ketamine combination was found to confer hemodynamic stability during spinal anesthesia as compared to propofol alone.

KEY WORDS: Spinal anaesthesia; Sedation; Propofol; Ketamine; Circulatory responses
Article Type: Report
Subject: Propofol (Health aspects)
Propofol (Research)
Hemodynamics (Research)
Heart beat (Physiological aspects)
Heart beat (Research)
Ketamine (Health aspects)
Ketamine (Research)
Authors: Nengroo, Showkat
Lone, Abdul Qayoom
Naqash, Imtiaz
Pub Date: 07/01/2011
Publication: Name: Internet Journal of Medical Update Publisher: Dr. Arun Kumar Agnihotri Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 Dr. Arun Kumar Agnihotri ISSN: 1694-0423
Issue: Date: July, 2011 Source Volume: 6 Source Issue: 2
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: India Geographic Code: 9INDI India
Accession Number: 261951344

Regional Anaesthesia is becoming an increasingly important aspect of anaesthesia practice. It offers several benefits to the patients including cardiovascular and respiratory stability, preservation of airway reflexes and rapid postoperative recovery (1). Some of the drawbacks of regional anesthesia however include fear of needles and pain at the puncture site (2) and recall of the procedures (3). These factors stress the importance of sedation during surgical procedures done under regional anaesthesia. Sedation has been shown to increase patient satisfaction during regional anaesthesia and may be considered as a means to increase the patient acceptance of regional anaesthetic techniques (4).

An ideal sedative is one that safely provides relief from pain, anxiety and unpleasant memories for a wide variety of procedures. Several sedative and analgesic drugs have been used singly or in combination (5-8) but no one regimen meets all of the above requirements.

Propofol, a phenol derivative produces dose-dependent sedation, hypnosis, anxiolysis and amnesia as well as possessing antiemetic properties (9), but it lacks analgesic properties and may not produce reliable amnesia at sub-anaesthetic doses (10). On the other hand, ketamine a phencyclidine derivative when used in sub-anaesthetic doses produces analgesia while preserving airway patency, increases heart rate and arterial blood pressure by activation of the sympathetic nervous system and reduces the incidence of spinal anaesthesia induced hypotension (11).

Propofol and ketamine administered in combination from separate syringes has been used successfully in a variety of settings including spinal anesthesia (12). This combination has been favored because of the opposing hemodynamic and respiratory effects of each drug (9). The combination has also been shown to reduce the dose of propofol required to achieve sedation (13) and is believed to result in less toxicity than either drug alone because their complementary effects enable the use of lower doses of each drug (14).

With this background we decided to compare the effect of propofol-ketamine combination to propofol alone on hemodynamics when used as a sedative adjuvant to spinal anaesthesia.


After approval from the hospital ethical committee and written informed consent from the patients, 60 ASA physical status I and II patients of either sex, aged 18 to 75 years undergoing spinal anesthesia for urological procedures were enrolled for the study. Patients with a history of allergic reaction to propofol and ketamine, obesity, significant central nervous system, cardiac, pulmonary, hepatic and renal disease were excluded from the study. Patients were randomly allocated to two groups of 30 patients each. Group I (propofol-ketamine combination group) and Group II (propofol alone group). The patients were premedicated with tablet Alprazolam 0.25mg in the morning on the day of the surgery.

On arrival to the operating room, patients were connected to Datex cardiocap monitor for monitoring of ECG, heart rate and NIBP. O2 saturation was monitored with Pace-Tech pulse oximeter. Baseline measurements of heart rate, systolic and diastolic blood pressures were recorded prior to administration of spinal anesthesia and then at 5 minutes intervals for first 30 minutes of surgery and every 15 minutes thereafter till a total duration of 90 minutes. After preloading the patients with 6ml/kg of Ringer lactate, spinal anesthesia was given with hyperbaric bupivacaine 0.5% in sitting position using 24 G spinal needle, in doses sufficient to provide a satisfactory sensory block for the procedure to be done. The sensory block was evaluated after every 3 minutes using a cold swab until the level was sufficient for the surgery to begin.

Immediately after spinal anesthesia, patients assigned to group I received an intial loading dose of propofol 0.4mg per kg and ketamine 0.1mg/kg followed by a continuous infusion of 1.2mg/kg/hr propofol and 0.3mg/kg/hr of ketamine. Group II patients received a bolus of 0.5mg/kg of propofol only followed by a continuous infusion of 1.5mg/kg/hr. The study drugs (Propofol or admixture of propofol-ketamine) were prepared by an anesthesiologist not involved in the study and the anesthesiologist assessing the level of sedation was blinded to the sedative infusion being administered. The level of sedation was recorded every 5 minutes and subsequent infusion rates titrated to maintain the sedation score at or around level 3 on a five point sedation score as shown in table I. The sedative infusion was stopped during the surgical procedure if the respiratory rate fell to less than eight breaths per minute, the infusion otherwise was discontinued at the end of surgical procedure. Total sedative and vasopressor requirements were noted. Oxygen was administered through a face mask to those patients who exhibited a Sp[O.sub.2] of 95% or less. Observations were continued in the recovery room till a total duration of 90 minutes from the start of surgery. Patients remained in the recovery room until sensory functions returned to normal.

The data was collected, tabulated and statistically analyzed using the student's t-test. Values were expressed as mean [+ or -] SD and a p value of <0.05 was taken as significant and p <0.001 as highly significant.


The patient data was comparable between the two groups on the basis of age, weight and sex distribution (Table 2). Duration of surgery was shorter in group II as compared to group I. The total dose of propofol administered was similar in both the groups (95 [+ or -] 35mg and 100 [+ or -] 40mg in groups I and II respectively), while as in group I, patients received additional 22 [+ or -] 11mg ketamine combined with propofol. The sedation scores showed no significant difference between the two groups with constant degree of sedation being maintained throughout the procedure. Four patients in group II experienced a hypotensive episode and needed ephedrine supplementation for treatment of hypotension.

Changes in heart rate and arterial blood pressure after the spinal anesthesia and sedative administration are shown in figure 1. It has been observed that the changes in the heart rate in the two groups did not differ significantly at predetermined intervals during the procedure. On the other hand both systolic and diastolic blood pressures remained significantly higher in group I patients, when compared to group II patients at similar time intervals. There were no significant differences in respiratory rate, Sp[O.sub.2] and the need for oxygen supplementation between the two groups.


Spinal anesthesia is one of the commonest techniques of regional anesthesia. The impediments to the effective use of spinal anesthesia are the predictable decreases in arterial blood pressure and heart rate through the accompanying sympathectomy with its attendant vasodilatation and blockade of cardio accelerator fibres. Another clinically important impediment to successful block is inadequate sedation.

The goals of sedation during spinal anesthesia are to provide an adequate level of sedation while minimizing pain and anxiety, maximizing amnesia, minimizing the potential for adverse drug-related events, controlling behavior, and maintaining a stable cardiovascular and respiratory status.

Propofol infusion provides excellent sedation during spinal block. The advantages to its use are that the technique is safe, simple, depth of sedation can be easily altered and recovery is within 5 minutes after stopping the infusion (14). However it has some properties that limit its usefulness. It causes reduction in myocardial contractility and in peripheral vascular resistance, leading to reduction of mean arterial pressure. However, ketamine has a stimulant effect on intact sympathetic nervous system which may offset the depressant effect of propofol.

A number of studies have demonstrated that the combination of ketamine and Propofol for sedation is safe and effective. The combination of the two agents appears to reduce side effects of each medication used alone, and allows for a rapid recovery time (15). Hence we decided to evaluate the effectiveness of the propofol-ketamine combination for sedation and maintenance of stable hemodynamics. We observed that propofol-ketamine combination as an infusion provided a comparable sedation to propofol only and the hemodynamics remained stable during spinal anaesthesia with propofol-ketamine infusion as compared to patients receiving propofol only.

Our results correlate with those of Frizelle et al who demonstrated that propofol-ketamine combination, given as infusion during spinal anesthesia, provided hemodynamic stability (12). Similar results were also obtained by Guit et al, who recommended propofol-ketamine combinations for TIVA also when stable hemodynamics are required (16).

Hemmingsen et al in their study observed that during spinal anesthesia patients could be kept hemodynamically stable by intravenous administration of ketamine (11).


We conclude that although propofol infusion in sub-anesthetic doses is an effective sedative adjuvant during spinal anesthesia, the propofol-ketamine combination has definite advantages over propofol alone for providing hemodynamic stability during spinal anesthesia.



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(16.) Guit JB, Koning HM, Coster ML et al. Ketamine as analgesic for total intravenous anaesthesia with propofol. Anesthesia. 1991 Jan;46(1):24-7.

Showkat Nengroo * ([PSI]) MD, Abdul Qayoom Lone ([dagger]) MD and Imtiaz Naqash ([double dagger]) MD

* Assistant Professor, ([dagger] Additional Professor, ([double dagger]) Professor, Department of Anesthesiology and Critical Care, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India

(Received 10 March 2010 and accepted 23 December 2010)

* Correspondence at: Department of Anesthesiology and Critical Care, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India; Email:
Table 1: Sedation Score

Score    Degree of Sedation

1        Fully awake and oriented
2        Drowsy
3        Eyes closed but arousable to command
4        Eyes closed but arousable to mild physical stimulation
5        Eyes closed but unarousable to mild physical stimulation

Table 2: Demographic variables of the patients
in the two groups

                            Group I              Group II

Number                         30                   30
Age (yrs)              57.63 [+ or -] 7.98    57.87 [+ or -] 6.69
Weight (Kg)            56.86 [+ or -] 6.64    57.53 [+ or -] 5.86
Sex (M/F)                     27/3                 27/3
Surgical time (min)       59 [+ or -] 13         42 [+ or -] 27
Total Propofol (mg)       95 [+ or -] 35        100 [+ or -] 40
Total Ketamine (mg)       22 [+ or -] 11              --
Sedation score          2.93 [+ or -] 0.82     2.82 [+ or -] 0.72
Ephedrine required            None                  4
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