European Journal of Cardiovascular Medicine

Nalbuphine belongs to mixed agonist– antagonist opioid analgesic group. It is agonist at kappa opioid receptors and a weak antagonist at mu opioid receptors. Nalbuphine is a potent analgesic and its analgesic potency is equivalent to that of the morphine. ^1-2

Nalbuphine by its action on kappa opioid receptors inhibit release of neurotransmitter substance P that mediates pain. In addition it acts as post synaptic inhibitor on the interneuron and output neuron of the spinothalamic tract which transports nociceptive information. Thus, when nalbuphine administered along with bupivacaine will have synergetic effect, thus prolonging the duration of sensory blockade without affecting sympathetic blockade and motor blockade. ³

Nalbuphine may produce similar degree of respiratory depression as that of morphine. However, nalbuphine exhibits ceiling effect such that increase does more than 30mg does not produce any further respiratory depression. Nalbuphine hydrochloride has potent opioid antagonist activity at doses equal to or lower than its analgesic does. ⁴

Hence, when administered with mu agonist opioids such as morphine, oxymorphone, fentanyl it may reverse or block opioid induced respiratory depression from the mu agonist analgesic.

Bupivacaine action is similar to any other local anaesthetics. The local anaesthetic primarily acts on the cell membrane of the axon on which it produces electrical stabilization. To prevent propagation of impulse large transient increase in permeability to sodium ion is necessary. Therefore, the resting membrane potential is maintained and depolarization in response to stimulation is inhibited.

The present study was conducted in department of Anesthesia in Sapthagiri Institute of Medical Sciences and Research Centre. After obtaining institutional ethical clearance and written informed consent from the patients and having met inclusion and exclusion criteria, 60 ASA grade I and II patients undergoing lower abdominal surgeries were randomly allocated into two groups. Group A received 3ml of 0.5% hyperbaric bupivacaine with 400 mcg inj. Nalbuphine. Group B received 3ml of 0.5% hyperbaric bupivacaine with 0.5 ml of normal saline.

The inclusion and exclusion criteria will be as follows.

Inclusion Criteria: 

1. ASA grade 1 and ASA grade 2
2.  Age between 18 to 50 years 
3.  Patients undergoing lower abdominal surgeries under spinal anaesthesia for 1 to 2 hours.

Exclusion Criteria: 

• Patient not giving consent
• Parturient

• Allergic to the study drugs 
• Patients on chronic opioid usage.
• Patients with  other co morbidities
• Patients having contraindications for sub arachnoid block

SAMPLE SIZE:

n = 2(Z_α +Z _β)²σ²/d²

N is the total sample size

Z_α – 95% of confidence interval (1.96)

Z _β – 80% of power (0.84 )

σ is the standard deviation 

d is the difference of means. 

N = 6(since the sample size obtained was small, 30 in each group was studied)

Randomised control trial.

 Randomization was done into two groups by computer generated method. The study drug was prepared by a senior anaesthetist not involved in procedure. Patients and anaesthesia providers were not aware of study drug.

Group A: Inj. bupivacaine hyperbaric 0.5% 3 ml + Inj.Nalbupine 400mcg with normal saline to 3.5ml

Group B: Inj. bupivacaine hyperbaric 0.5% 3 ml+ 0.5ml normal saline to 3.5ml

Baseline investigations - CBC, Blood group, Blood Glucose, Electrocardiogram, Chest X ray as per the standard guidelines were obtained                                                                             

Pre operatively patients were cannulated with 18G IV cannula were preloaded with 10 ml/kg of ringer’s lactate solution. Standard monitors were connected such as pulse oximetry, ECG, NIBP and baseline values were noted.

Under all aseptic conditions, subarachnoid block was performed using 25G Quinke’s spinal needle at L3 –L4 level in sitting position. Study drugs were injected to the respective group. Hemodynamic parameters namely heart rate, systolic blood pressure, diastolic blood pressure and oxygen saturation were monitored every 5mins for half an hour, every 10 mins for next 1 hour and every 20mins throughout the surgical procedure. 

Following parameters were observed and noted:

1– Time of Sub arachnoid block. 

2– Time of onset of sensory blockade. 

The onset of sensory blockade was taken as the time taken from the injection of the drug to sensory block up to T10.

3– Time of onset of motor blockade.

The onset of motor blockade is taken as the time taken from injection of the drug to time taken to reach modified Bromage score of 3.

4– Maximum Height of sensory blockade. 

The maximum height of sensory block is considered as height of sensory block achieved at the end of 30 min.

5– duration of sensory blockade. 

Duration of sensory blockade is defined as two dermatome regression of anaesthesia from the highest level achieved.

6– duration of motor blockade

Duration of motor blockade is taken as the time for  return to Modified Bromage Score of

7– duration of post operative analgesia based on VAS score

In the postoperative period VAS score was calculated on a 10-cm  scale with ‘0’ on one end, meaning ‘no pain at all’, while ‘10’ on the other end representing ‘worst pain imaginable’. Patients rated the degree of pain by making a mark on the scale. Thus, the pain score was obtained by measuring the distance from the ‘0’ end to the indicated mark. 

Postoperative rescue analgesic drug was given when patient’s VAS score reached 3 (this time was taken as duration of postoperative analgesia). Inj. diclofenac 75 mg in 100ml saline was given IV as rescue analgesia. All the parameters studied were observed and noted. 

MODIFIED BROMAGE SCALE:

 0-able to move hip, knee, ankle and toes (0%)

 1-Inability to raise extended leg but able to move knee and feet (33%) (Partial)

 2-Inability to raise extended leg and move knee but able to move feet (66%)

 3- Unable to move hip, knee and ankle (100%) (Complete block)

 Motor block is measured postoperatively for every 1 hour till the Modified Bromage Score is 0.

 Perioperatively patients will be observed carefully for the side effects like  bradycardia, hypotension, )  respiratory depression, nausea, vomiting, itching. Inj. Atropine 0.6 mg was given if Heart rate was <50 bpm, Inj. Ephedrine 6mg was given if mean aterial pressure was <65 mmhg.

All the parameters studied were observed and noted. The Students unpaired‘t’ test was used to compare quantitative variables in both groups. The qualitative variables was compared using students paired‘t’ test for each group. The categorical data were compared using Chi square test. Data are mean (standard deviation) unless otherwise specified. Significance is taken as p value < 0.05.

The study was conducted in Department of Anaesthesiology, Sapthagiri Institute of Medical Sciences and Research Centre .The study was conducted on 60 ASA grade I and II patients undergoing lower abdominal surgeries.

Randomization was done into two groups by computer generated method.

Group A: Inj. Bupivacaine hyperbaric 0.5% 3 ml + Inj. Nalbuphine 400mcg diluted  with normal saline

Group B: Inj. Bupivacaine hyperbaric 0.5% 3 ml + Normal saline 0.5ml. The results obtained were tabulated and analysed

The duration of postoperative analgesia was significantly prolonged in Nalbuphine group (222.93+/- 19.75 min) than in control group (151.64+/- 18.42 min) which was statistically significant. Hemodynamic parameters were comparable between the two groups with no major side effects or complications.

Graph1: Mean Weight

Graph.2 Mean Height

Table 1:  Mean duration of post operative analgesia (in minutes)

Graph.3

Table 2: Comparison of mean heart rate between two groups ( bpm )

Table.3: Comparison of mean of Mean Arterial Pressure (MAP) between two groups ( mmhg )

Spinal anaesthesia is one of the most preferred anaesthetic technique, because of its simplicity, rapid onset of action, adequate sensory and motor blockade and fewer complications.

The addition of opioids to local anaesthetics is the most common method to prolong the duration of sub arachnoid block.

Adequate analgesia in postoperative period not only prevents adverse effects associated with pain, but also maintains normal respiratory function preventing infection, atelectasis and provides better wound healing.

Intrathecal opioids causes segmental analgesia by binding to opioid receptors in dorsal horn of the spinal cord. They prolong duration of analgesia without affecting motor or autonomic nervous system function. Their combination with intrathecal local anaesthetics limits regression of sensory blockade which is seen with local anaesthetics alone. Therefore, opioids reduce the dose requirement of local anaesthetics and also provide significantly extended postoperative analgesia without prolonging the recovery.

Nalbuphine is an opioid structurally related to oxy- morphine. It is a highly lipid soluble opioid with agonist action at kappa opioid receptors and antagonist action on mu opioid receptors. They have short duration of action consistent with their lipid solubility and rapid clearance compared with other opioids like morphine.

The present study was conducted in the department of Anaesthesiology, Sapthagiri Institute of Medical Sciences and Research centre. In the study 60 patients of ASA gradeI and II undergoing lower abdominal surgeries were randomly divided into two groups. In group A patients received 3 ml of 0.5% Inj. Hyperbaric Bupivacaine with 400mcg of Inj. Nalbuphine , and in group B patients received 3ml of 0.5% Inj. Hyperbaric bupivacaine with 0.5ml normal saline intrathecally. The demographic data in both the study group and control group was comparable with respect to height, weight, age, sex, mean duration of the surgery and type of surgery.

In our study duration of postoperative of analgesia was significantly prolonged in Nalbuphine group (222.93+/- 19.75 min) than in control group (151.64+/- 18.42 min). In a similar study, Rashmi Dubey et al5., observed the mean duration of analgesia was 366+/- 15.5 min in nalbuphine group and 159.5+/-18.42 min in control group.

In a similar study, Mostafa H et al6., observed that duration of analgesia was more in Nalbuphine group (166.33+/- 14min) compared with fentanyl group (150.83+/- 13 min).

Nalbuphine by its action on kappa opioid receptors inhibits release of neurotransmitter substance P that mediates pain. In addition it acts as post synaptic inhibitor on the interneuron and output neuron of the spinothalamic tract which transports nociceptive information.

Local anaesthetics acts by inhibiting voltage gated sodium channels thus interrupting sodium influx, which lead to inhibition of action potential and therefore inhibition of signal conduction. The principle site of action of local anaesthetics placed in lumbar subarachnoid space is preganglionic fibers as they leave spinal cord in the anterior rami.

Thus, when nalbuphine administered along with bupivacaine will have synergetic effect, thus prolonging the duration of sensory blockade without affecting sympathetic blockade and motor blockade.

In our study, patients in both the groups had similar haemodynamic results without any adverse effects similar to results observed in studies by Culebras et al7 and Mostafa H et al.

According to study by Thomas et al8., to compare respiratory depression and analgesic effect between equipotent doses of morphine and nalbuphine, observed that nalbuphine exhibit ceiling effect of analgesia and any further increase in the dose had similar intensity of analgesia.

Thus, in our study by adding 0.4mg of Nalbuphine to hyperbaric bupivacaine and given intrathecally, significantly prolonged the duration of blockade  when compared with hyperbaric bupivacaine alone..

In conclusion, addition of Inj. Nalbuphine (400mcg) to 3 ml of 0.5% hyperbaric bupivacaine has significantly prolongs duration of postoperative analgesia, compared to 3ml of 0.5% hyperbaric bupivacaine only without any significant adverse effects. The dose used was chosen according to the physical characteristics of patients in our study. However, comparative study with different doses could be studied. To identify the ideal adjuvant, comparative study with different type of    drugs    can be carried out.

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