COMPARISON OF INTRATHECAL“FENTANYL+BUPIVACAINE” AND “KETAMINE+BUPIVACAINE”FOR SPINAL ANESTHESIA – RANDOMIZED PROSPECTIVE DOUBLE BLIND STUDY

 

ASHOK SHANKAR BHADE MD, MAHESH NAGAPPA MD

Ashok Shankar Bhade MD, Professor and HOD
Mahesh Nagappa MBBS, MD Senior Resident
Department of Anaesthesiology and Critical Care
Jawaharlal Institute of Postgraduate Medical Education and Research
Pondicherry 605006
India

Abstract

Background: This double blind study was designed to compare the cardiorespiratory stability and the incidence of side effects after intrathecal administration of ketamine-bupivacaine and fentanyl-bupivacaine for lower abdominal and lower limb surgeries.
Method: Eighty ASA physical status 1 or 2 patients scheduled to undergo elective lower abdominal and lower limb surgeries under subarachnoid block were included in the study following approval from the institute ethics committee. Patients were randomly allocated to group K (ketamine, n=40) or group F (fentanyl, n=40) by the sealed envelope technique after taking an informed consent.
Results: Intrathecal ketamine with bupivacaine as compared to fentanyl with bupivacaine produced faster onset of sensory block, longer duration of analgesia and longer duration of post-op analgesia (63.1sec vs 69sec, 108.2min vs 98.4min, 176.1min vs 141,3min, respectively) P<0.05 with better hemodynamic stability. The incidence of nystagmus is more with intrathecal ketamine and pruritis is more with intrathecal fentanyl (40%vs 0%, 0% vs 30% respectively).
Conclusion: Intrathecal ketamine is a better adjuvant to Bupivacaine than intrathecal fentanyl in patients undergoing lower abdominal and lower limb surgeries under subarachnoid block.

Key Words:

Ketamine, fentanyl, subarachnoid block.

Spinal Anaesthesia is used extensively for lower abdominal surgeries and lower extremity surgeries, because it has distinct advantages over general anaesthesia. Lignocaine and Bupivacaine are the commonly used local anaesthetic agents for spinal Anaesthesia. The adjuvants like opioids and ketamine are sometimes combined with Local Anaesthetic for Spinal Anaesthesia.The rationale for combining adjuvants to local anaesthetic drugs is to lower the dose of each agent, and maintaining analgesic efficacy whilst reducing the incidence and severity of side effects.
Spinal local anaesthetics and opioids have synergistic antinociceptive effects, and the opioids have been shown to decrease the requirement of local anaesthetics and to reduce the incidence of hypotension. Intrathecal Ketamine has beneficial effect on cardiorespiratory functions and has good analgesic and local anaesthetic effects. Intrathecal Ketamine has central sedative effect and so the patient does not suffer from hallucination and irritability.
The present study is designed to evaluate whether the choice of Adjuvant solution could affect the block characteristic and also to know if one preparation has advantage over the other.

Materials and Methods

Eighty ASA physical status 1 or 2 patients, in the age group of 15 to 60 years, scheduled to undergo elective lower abdominal and lower limb surgeries under subarachnoid block were included in the study following approval from the institutional ethics committee. Patients with height <145cm, any contraindication to spinal anesthesia, or patients with History of pruritis or allergy to opioids/local anaesthetics/Ketamine and Patients who have received sedative medications in the last 4hrs or patients on antipsychotic drugs were excluded. Patients were randomly allocated to group K (25mg, Preservative free Ketamine, 0.5ml and 0.5% Bupivacaine 2.0ml, n=40) or group F (25μg Fentanyl, 0.5ml and 0.5% Bupivacaine 2.0ml, n=40) by the sealed envelope technique after taking informed consent. Parameters studied are
? Onset of sensory level (checked at 30sec interval with 24 gauge needle at T12 dermatome by pin prick method).
? Maximum level of sensory blockade (Sensory level will be noted at 2 minutes interval till 3 consecutive level seen to be the same with no further rise).
? Maximum intensity of motor blockade as assessed by Bromage score.

Bromage Score:
1. No impairment of movement of legs and feet
2. Barely able to flex knees, no impairment in movement of feet
3. Unable to flex knees, barely able to move feet
4. Unable to move knee or feet.

? Duration of Analgesia (four segment regression time).
? Haemodynamic changes (SBP, DBP, Mean BP and Heart rate)
? Respiratory changes (Respiration rate and Saturation)
? Degree of sedation as assessed by “JIPMER Sedation score”

1. Agitated and uncomfortable
2. Awake and comfortable
3. Sleeping intermittently
4. Asleep but wakes up to touch
5. Asleep, but arousable on painful stimulus.

? Incidence of side effects (Nausea, Vomiting, Pruritis, Shivering and Nystagmus).
Eighty patients who fulfilled the eligibility criteria were chosen and explained about the procedure and consent taken. Patients were subsequently randomized by the sealed envelope technique into two groups of 40 each.

After securing IV (18G) access and routine monitoring, patient were placed in the left lateral position and preloaded with 500ml of Ringer’s lactate solution over 10min. A baseline recording of Heart rate, NIBP, RR, SPO2 were recorded using Datex Ohmeda S5 monitor. After ensuring the table in horizontal position, 2.5ml of study drug will be injected over 15sec in the L3-L4 interspace with 25G quinke’s type spinal needle using standard sterile technique.

Onset of sensory level, peak sensory level, and motor blockade will be noted. NIBP, Heart rate, Respiration rate & Hemoglobin oxygen saturation will be recorded at 2, 5, 10, 15, 20, 30, 60, 90,120 min. Sedation will be assessed, using JIPMER sedation score. Incidence of Nausea, Vomiting, Shivering, Pruritis, and Nystagmus will be noted.
Intraoperative fluid replacement will be given as necessary, depending
on the blood loss and haemodynamic parameters. All fluids used will be at room temperature and no extra covering will be used to provide warmth unless the patient complaints of shivering. Fluid balance and usage of vasopressors, atropine, opioids or perinorm will be recorded.

Table tilt will not be altered before 10 minutes after spinal. A head
down tilt will be given if a minimum analgesic level of T10 is not attained by this
time. Parametric data were analyzed using Independent student’s sample t test and Non-parametric data were analysed using Mann Whitney U test. P < 0.05 was considered significant.

Results

Eighty ASA 1 or 2 patients scheduled to undergo lower abdominal and lower limb surgeries were randomly allocated into group K ( ketamine, n= 40) and group F (fentanyl, n= 40). After preloading with five hundred ML of lactated Ringer’s solution, subarachanoid block was established with a 25 Gauge spinal needle at L3 L4 interspace using 2ml of 0.5% hyperbaric Bupivacaine with 25 mg (0.5ml) preservative free ketamine in group K and 2ml of hyperbaric Bupivacaine with 25 µg (0.5ml) of fentanyl in group F.

 

Table 1: Physical characteristic and Baseline Parameters

S. NO.	Parameter	Group K (n = 40)	Group F (n = 40)
1.	Age (Years)	41.1 ± 11.2	39.1 ± 9.2
2.	Weight (Kg)	52.5 ± 4.8	52.9 ± 5.4
3.	Height (Cm)	154.9 ± 3.3	155.1 ± 5.1
4.	Systolic blood pressure (mmHg)	123.3 ± 13.8	116.9±10.0*
5.	Diastolic blood pressure (mmHg)	74.1 ± 7.8	76.4 ± 6.7
6.	Mean arterial pressure (mmHg)	90.5 ± 8.3	89.9 ± 7.1
7.	Heart rate (beats/min)	92.4 ± 14.0	100.9 ±14.6*
8.	Respiratory rate (rate/min)	15.4 ± 3.1	16.3 ± 2.6
9.	Hemoglobin Oxygen Saturation (%) #	99 (93- 100)	99 (94-100)

 

 

Mean ± SD,    # Median (range) * P<0.05

Table 2 : Data of patients with Significant Hypotension

S.NO.	Parameter	Group K (n = 40)	Group F (n = 40)
1.	Incidence	20%	37.5% *
2.	Time to Onset (min)	15.0 ±  5.9	24.3 ± 5.6*
3.	Fall in MAP (%)	23.0 ± 2.9	25.9 ± 6.1

Mean ± SD

* P<0.05

           

Table 3: Data of Sensory block

S. NO.	Parameter	Group K (n = 40)	Group F (n = 40)
1.	Onset (Sec)	63.1 ± 2.5	69.0 ± 3.6*
2.	Sensory level #	T4 (T3-T5)	T4 (T3-T5)
3.	Duration (min)	108.2 ± 4.6	98.4 ± 14.8*
4.	Time for first analgesic (min)	176.1 ± 13.4	141.3 ± 6.8*

Mean ± SD, # Median (range)

 

 

 

A median sensory level of T4 was observed in both the groups but the incidence of hypotension was markedly lower in group K when compared to the group F (20% Vs 37.5%), P<0.05. Among the hypotensive patients, the mean percentage change in mean arterial pressure was similar in both the groups (23% vs 25.9%), but the time to maximum fall in mean arterial pressure was earlier in group K than group F (15 min Vs 24.3min) P<0.05. The statistically significant mean percentage fall in the heart rate occurred earlier in group F than group K (5th minute vs 20th minute) and the severity of the mean percentage fall in the heart rate was more in group F (30.25 ± 1.64) than group K (26.33 ± 1.46), but was statistically not significant.
The onset of sensory block was earlier in group K than group F, (63.1secs Vs 69 secs), p value <0.05.The duration of sensory block and the duration of postoperative analgesia was longer in group k (108.2min and 176.1min respectively) than in group F (98.4min and 141.3min respectively), P<0.05. The incidence of nystagmus was higher in group K (40%, P<0.05), where as the incidence of pruritis was higher in group F (30%, P<0.05). The incidence of vomiting was same in both the groups, whereas the incidence of shivering was more in fentanyl group (10% Vs 2.5%)

Discussion

Ketamine, a phencyclidine derivative, popularly used as a general anesthetic has been used for spinal anesthesia with claims of advantages. It is widely accepted that intrathecal injection of ketamine is safe. In our study we evaluated the effect of ketamine and fentanyl as adjuvant for spinal anesthesia. This study was conducted in Jawaharlal Institute of Post Graduate Medical Education and Research from the month of August 2005 to August 2007. Eighty patients posted for lower limb and lower abdominal surgery were included in the study following approval from the institute’s ethics committee. They were randomly allocated to two groups of forty each. Patients belonging to Group K received 25mg (0.5ml) of preservative free ketamine and 2ml of 0.5% Bupivacaine whereas patients belonging to Group F received 25µg (0.5ml) of fentanyl and 2ml of 0.5% Bupivacaine.

The mean age in group K was 41.1 ± 11.2 years and 39.1 ± 9.2 years in group F. The mean weight in group K was 52.5 ± 4.8kg and group F was 52.9 ± 5.4kg. The mean height in group K was 154.9 ± 3.3cm and group F was 155.1 ± 5.1cm. The physical characteristics were comparable between the groups.

In the group K, there was statistically significant decrease in the heart rate compared to the baseline value from 20th minute to 120th minute (P<0.05). In the group F, there was statistically significant decrease in the heart rate compared to the baseline value from 5th minute to 120th minute (P<0.05).The statistically significant mean percentage fall in the heart rate occurred earlier in group F than group K (5th minute vs 20th minute) and the severity of the mean percentage fall in the heart rate was more in group F (30.25 ± 1.64) than group K (26.33 ± 1.46), but was statistically not significant. When compared between the groups, the mean percentage fall in heart rate from the base line value was statistically significant in group F between the 2nd and 20th minute (P<0.001) following subarachnoid block. The decrease in the heart rate in both groups in our study was probably because of deeper level of sedation. These observations are similar to other studies 10, 13, 27.

In the group K, there was statistically significant decrease in the mean arterial blood pressure compared to the baseline value from 10th minute to 30th minute (P<0.05). In the group F, there was statistically significant decrease in the mean arterial blood pressure compared to the baseline value from 5th minute to 120th minute (P<0.05). When compared between the groups, the mean percentage fall in mean arterial pressure from the base line value was statistically significant in the group F at 2nd min and from 15th minute to 120th minute (P<0.05) following subarachnoid block.
A significantly high incidence of hypotension was observed in group F (37.5%) when compared to group K (20%), P< 0.05. Hypotension occurred at 15th minute and 24th minute following the subarachnoid block in group K and group F respectively. The Mean percentage change in Mean Arterial Pressure was similar in both the groups. The lower incidence of hypotension in the ketamine group can be explained on the basis of property of ketamine to release catecholamine irrespective of the dose given10. 13, 27
Fentanyl group showed a slight reduction in respiratory rate throughout the study period as compared to ketamine group which was not clinically significant, but change in respiratory rate was statistically significant at the 90th min, P<0.05. This may be probably because of the central respiratory depressant action of intrathecal fentanyl23. The change in respiratory rates was not significant within the groups and there was no episode of desaturation during the study period. Bion 27 also stated that intrathecal ketamine does not change the respiratory rate significantly. Other studies also confirm that there is no bradypnea with intrathecal ketamine.

In our study the onset of sensory block was earlier in group K (63.1 sec), when compared to group F (69.0 sec, P<0.05). Bansal et al26 also reported similar onset of action. The duration of sensory block (Four segment regression time) and duration of post operative analgesia (Time for first request of systemic analgesia) were longer in group K (108.2 min and 176.1min respectively),when compared to group F (98.4min and 141.3min respectively), P<0.05. The axonal conduction block produced by the ketamine could be partly responsible for this effect 8. The longer duration of action in the ketamine group may be explained on the basis of slow release of ketamine (liposomal impregnation) 10, 28, 29. The addition of Ketamine to local anesthetic or other analgesics in peripheral or neuraxial anesthesia and analgesia improves or prolongs pain relief (Level II evidence) 14.

The median Bromage score and Sedation scores were similar in both the groups. These observations are similar to other studies10. In our study the incidence of nystagmus was 40% in the ketamine group which is quite low as compared to the study of Bansal et al 26 (>80%). The decreased incidence is probably because of lower doses of ketamine used in our study. The high incidence of nystagmus observed in group K (40%) as compared to group F (0%, P<0.05) can be explained on the basis of central side effects of ketamine.

The incidence of pruritis in group F (30%) when compared to group K (0%, P<0.05) can be explained on the basis of side effects of intrathecal opioids. Pruritis induced by intrathecal opioid is likely due to cephaloid migration of the drug in the cerebro-spinal fluid and subsequent interaction with the trigeminal nucleus located superficially in the medulla. The opioid receptors are present in the trigeminal nucleus and the trigeminal nerve roots. The itch centre located in the lower medulla indicates that the trigeminal nucleus is involved in the itch reflex.
The incidence of vomiting was similar in both the groups (10%) whereas the incidence of shivering more in the fentanyl group (10%) than the ketamine group (2.5%), these were found to be not statistically significant.

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