European Journal of Cardiovascular Medicine

Postoperative nausea and vomiting (PONV) are among the most common complaints that can occur after general anaesthesia.¹ PONV is defined as any nausea, retching or vomiting that occurs within first 24 hours postoperatively.² Nausea is a subjective unpleasant sensation which is associated with awareness of the urge to vomit.¹ Retching is defined as rhythmic and spasmodic contraction of respiratory muscles like diaphragm, chest wall muscles and abdominal muscles without expulsion of any gastric contents.¹ Vomiting is defined as forceful expulsion of gastric contents through mouth which is brought about by powerful and sustained contraction of abdominal muscles, opening of the gastric cardia and descent of diaphragm.¹ PONV if not treated can lead to gastric aspiration, postoperative bleeding, wound dehiscence, electrolyte imbalance and delayed discharge particularly after outpatient surgeries.^1,3

There are multiple factors affecting PONV which can be - non anaesthetic and anaesthetic. Non anaesthetic factors include patient related factors, operative procedure and duration of surgery. Patient related factors are- age, gender, obesity, history of motion sickness or history of previous PONV, anxiety, non-smoking status and gastroparesis.^1,4,5 Surgery having duration more than 30 minutes is an independent risk factor for POV.⁶

Anaesthetic factors include pre-anaesthetic medication, anaesthesia techniques and postoperative factors like pain, dizziness, oral intake and use of opioids.1 Premedication with morphine and other opioids have been associated with increased risk of PONV. General anaesthesia is associated with more risk of PONV than the regional anaesthesia. Inhalation agents like N2O, cyclopropane, ether, halothane and induction agents like ketamine and continuous infusion of etomidate are associated with more incidence of PONV.^1,4,5,7

Corticosteroids like dexamethasone has shown to have a potent antiemetic activity. The first trial which suggested the role of dexamethasone in preventing PONV was published in 1993. The precise mechanism of antiemetic efficacy is still unknown. A common theory is prostaglandin antagonism. It may also inhibit the synthesis and release of 5-HT by depleting its precursor tryptophan or prevent the activation of its receptors in gastrointestinal tract through its anti-inflammatory properties. Moreover, it also releases endorphins and synergizes with other antiemetic drugs by sensitizing their receptors.³ Dexamethasone has delayed onset of action so timing of administration is also critical. Prophylactic preinduction administration is shown to be more effective than at the conclusion of surgery.⁸ Anaesthetic agents induce vomiting reflex by stimulating the central 5-HT3 receptors present in CTZ and by releasing serotonin from the enterochromaffin cells of small intestine followed by stimulation of 5-HT3 receptors on vagus nerve afferent fibers.^9,10,11

A wide range of dexamethasone (8-32 mg) has been used for prophylaxis of emesis related to chemotherapy and after gynaecological and paediatric surgeries. A dose of 8 mg dexamethasone is used frequently.¹²

Dexmedetomidine is highly selective alpha-2 receptor agonist. It is having sympatholytic, sedative, analgesic and opioid sparing properties. Intravenous dexmedetomidine also has 4 efficacy in improving perioperative hemodynamic stability and postoperative analgesia.¹⁴ It decreases the incidence of PONV by various mechanisms. It decreases the intraoperative consumption of anaesthetics and opioids, which decreases the risk of PONV. PONV may be triggered by high catecholamines concentration and dexmedetomidine decreases the sympathetic tone, so it decreases the risk of PONV. It also has direct antiemetic effect by activating the alpha-2 receptors.¹⁵ Minor side effects like hypotension and bradycardia can occur with dexmedetomidine.² It has been widely studied in patients undergoing laparoscopic surgeries for premedication¹⁶, anaesthetic adjuvant¹⁷, attenuation of hemodynamic response to pneumoperitoneum, prevention of postoperative side effects like PONV, shivering and pain.¹⁸

We performed a study to compare the effect of dexmedetomidine and dexamethasone on PONV after laparoscopic cholecystectomy under general anaesthesia.

The present study was conducted in the Department of Anaesthesiology and Critical Care, Pt. B. D. Sharma PGIMS, Rohtak in a prospective, randomised double blinded manner after obtaining approval from the institutional ethical committee and patient’s written, informed consent. The study included 70 patients of either sex of age 18-60 years, belonging to American Society of Anesthesiologists (ASA) physical status of I-II with scheduled for elective laparoscopic cholecystectomy under general anaesthesia.

Patients were randomly allotted to one of the two groups equally of 35 patients each, using random number table as follows: Group A (n=35): received an intravenous single dose of 1 mcg.kg-1 dexmedetomidine after induction of anaesthesia and before skin incision. Group B (n=35): received an intravenous dose of 8mg dexamethasone after induction of anaesthesia and before skin incision.

All statistical analyses were performed by using SPSS 22.0 software package (SPSS Inc., Chicago, IL, USA). All data was summarized as mean ± SD for continuous variables, numbers and percentages for categorical variables. The variables were assessed for normality using the Kolmogorov Smirnov test. A p≤0.05 was accepted as statistically significant.

In the Post Anaesthesia Care Unit (PACU) all the patients were monitored, received O2 via venturi mask. An anaesthesiologist blind to the study drug observed the patients for PONV, sedation, pain score and first analgesic rescue time. PONV was assessed at 2 h, 6 h, 12 h and 24 h based on the scale as described below PONV was assessed and graded as follows 26: Grade 0: No PONV Grade 1: Mild PONV Grade 2: Moderate PONV Grade 3: Severe PONV 20 Postoperative pain was graded using visual analogue scale; 31 - VAS 0; no pain, VAS 10; severe pain. Post-operative sedation was checked every 10 minutes in PACU and graded, using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) Score32, as: 0 = does not respond to pain 1 = does not respond to mild prodding or shaking 2 = responds only after mild prodding or shaking 3 = responds only after name is called out loudly and/or repeatedly 4 = lethargic response to name spoken in normal tone 5 = responds readily to name spoken.

Patients in all groups were comparable with respect to mean age, sex, ASA- grading, demographic profile and duration of surgery.

 Intraoperative Parameters.

Comparison of Heart Rate within and between groups

Inference:

There was decrease in heart rate after administration of dexmedetomidine within groups( p value < 0.05). and between two groups ( p value > 0.05)

Table II

Comparison of systolic blood pressure (SBP) within and between the groups

Comparison of systolic blood pressure (SBP) within the groups showed fall in systolic b.p after administration of dexmedetomidine (p value < 0.05)

 Comparison of systolic blood pressure (SBP) within the groups showed fall in systolic b.p after administration of dexmedetomidine (p value > 0.05).

Table III

Comparison of diastolic blood pressure (DBP) within and between the groups.

Comparison of Diastolic blood pressure (DBP) within the groups showed fall in diastolic b.p after administration of dexmedetomidine (p value = 0.001)

Comparison of diastolic blood pressure (DBP) within the groups showed fall in systolic b.p after administration of dexmedetomidine (p value > 0.05).

Table – IV

Comparison of SpO2 between two groups

Comparison of SpO2 between two groups: Baseline saturation of oxygen and before administration of drug were comparable between two groups (p value>0.05). There was no significant difference between two groups after administration of drugs, after extubation and shifting to recovery room (p value>0.05). 

Table -V

Incidence and severity of Postoperative Nausea and Vomiting (PONV)

p value=0.73

After 2 hours of surgery, 31.4% of patients experienced PONV in group A while in group B 34.3% of patients had PONV. It was not found to be statistically significant (p value=0.79). (Figure-13) In group A, 22.9% patients had grade 1, 8.6% patients had grade 2 and none had grade 3 PONV while in group B 25.7% had grade 1, 5.7% had grade 2 and 2.9% had grade 3 PONV (p value=0.73)

Table -VI

After 6 hours of surgery, incidence of PONV was found to be less in group A (25.7%) than in group B (31.4%). However, it was not found statistically significant (p value=0.59). (Figure13) In group A, 22.9% had grade 1, 2.9% had grade 2 and none had grade 3 PONV and group B 2.9% had grade 1, 22.9% had grade 2 and 5.7% had grade PONV. In group B severity of PONV was found to be more than in group A which was statistically significant (p value=0.005).

Table -VII

After 12 hours of surgery, incidence of PONV was 11.4% in group B while group A had no incidence of PONV. It was found to be statistically significant (p value=0.03). (Figure-13) In group A, no incidence of PONV was found after 12 hours of surgery while in group B 8.6% of patients had grade 1, 2.9% of patients had grade 2 PONV. In group B, severity of PONV was found to be more than group A after 12 hours of surgery however, it was not statistically significant (p value=0.12).

Table – VIII

After 24 hours of surgery, only 3 patients (8.6%) in group B had incidence of grade 1 PONV while no patient in group A had PONV. It was not found to be statistically significant (p value=0.07). We performed this prospective, randomized and double-blind study on 70 patients of either gender, aged 18-60 years, of ASA-PS grade I or II, posted for laparoscopic 37 cholecystectomy under general anaesthesia to compare the effect of dexmedetomidine and dexamethasone in prevention of PONV.

We performed this prospective, randomized and double-blind study on 70 patients of either gender, aged 18-60 years, of ASA-PS grade I or II, posted for laparoscopic 37 cholecystectomy under general anaesthesia to compare the effect of dexmedetomidine and dexamethasone in prevention of PONV.

Age: The mean age of the patients enrolled in group A was 38.43±8.925 and in group B, 38.14±7.593 years which was comparable in both the groups (p value>0.05). Gender: Our study included 9 males and 26 females in each group. Weight: The mean weight in group A was 63.66±7.392 and 62.14±9.617 kg in group B which was comparable between two groups. ASA Physical status: All patients included were either ASA grade I or grade II. Sinclair et al prospectively studied 17,638 consecutive outpatients who had surgery to identify the predictors of PONV where they found that among patients younger than 50 years, there was no association between age of patients and frequency of PONV but after 50 years of age, frequency of PONV had a marked linear decrease with increasing age. ASA I and II had higher rates of PONV than ASA III patients but it was not found to be an independent risk factor for PONV. Females had around two times higher rate of PONV when compared to males.²⁸ In our study, age, gender, weight and ASA PS were comparable in both the groups in contrast to this study.

Duration of surgery was comparable between group A (82.29±11.59 minutes) and group B (86±8.977 minutes). (p value=0.13) Duration of Anaesthesia: Duration of anaesthesia in group A was 96.571±11.68 and 98.71±7.07 minutes in group B which was comparable between two groups (p value=0.36). Sinclair et al prospectively studied 17,638 consecutive outpatients who had surgery to identify the predictors of PONV where they found a direct association between duration of anaesthesia and the risk of PONV. A 30 minutes increase in duration predicted a 59% increase in the incidence of PONV.²⁸ In our study, duration of surgery and anaesthesia were comparable between both the groups in contrast to this study. Heart Rate: Decrease in heart rate 15 minutes after administration of dexmedetomidine (12.6%), after extubation (11.29%) and in recovery room (10.6%) in group A was found to be more than in Group B 15 minutes after administration of dexamethasone (6.47%), after extubation (6.06%) and in recovery room (6.49%) respectively. However, it was not significant 38 statistically (p value > 0.05). None of the patients had severe bradycardia and required atropine to treat bradycardia. Systolic Blood Pressure: Fall in SBP in Group A, after 15 minutes of drug administration (11.43%), after extubation (9.106%) and in recovery room (8.83%) was found to be more than fall in Group B after 15 minutes of drug administration (5.55%), after extubation (4.55%) and in recovery room (5%). However, it was not statistically significant (p value > 0.05). Diastolic Blood pressure: There was more fall in DBP in group A 15 minutes after drug administration (13.15%), after extubation (10.05%) and after shifting to recovery room (10.05%) from baseline when compared in group B after drug administration (6.05%), after extubation (4.31%) and in recovery room (3.55%). However, it was not statistically significant (p value>0,05).

Kallio et al conducted a study to see the effects of dexmedetomidine on hemodynamic control mechanisms. Dexmedetomidine was administered to five healthy volunteers in a single intravenous dose of 12.5, 25, 50 and 75µg as a part of placebo-controlled study. Dose dependent decrease in systolic and diastolic blood pressure was observed and heart rate was decreased.30

In our study we observed that after 2 hours of surgery, Incidence of PONV in group A was 31.4% and 34.3% of patients in group B. In group A, 22.9% patients had grade 1, 8.6% patients had grade 2 and none had grade 3 PONV while in group B 25.7% had grade 1, 5.7% had grade 2 and 2.9% had grade 3 PONV. Incidence and severity of PONV were comparable after 2 hours of surgery. AT 6 HOURS In our study we observed after 6 hours of surgery, incidence of PONV was 25.7% in group A and 31.4% in group B. In group A, 22.9% had grade 1, 2.9% had grade 2 and none had grade 3 PONV and group B 2.9% had grade 1, 22.9% had grade 2 and 5.7% had grade PONV. 42 Incidence of PONV was comparable between two groups (p value=0.59), but severity of PONV was found to be significantly less in group A (p value=0.005). AT 12 HOURS After 12 hours of surgery, incidence of PONV was 11.4% in group B while group A had no incidence of PONV. In group B, 8.6% of patients had grade 1, 2.9% of patients had grade 2 PONV. Incidence of PONV in group B was significantly more (p value=0.03). Severity of PONV was more in group B but not found significant statistically (p value=0.12). AT 24 HOURS After 24 hours of surgery, only 3 patients (8.6%) in group B had incidence of grade 1 PONV while no patient in group A had PONV. It was not found to be statistically significant (p value=0.07). In our study, the incidence of PONV was comparable between two groups at 2h, 6h and 24h and found to be significantly more in group B at 12h (p value=0.03), The severity of PONV was comparable between two groups except at 6h (p value=0.05). The severity of pain was found to be less in dexmedetomidine group and sedation score was found to be more in dexmedetomidine group. Rescue therapy was considered in patients having two or more episodes of vomiting or retching, any nausea lasting for more than 30 minutes, whenever patient request for treatment or severe degree of nausea. Injection Ondansetron 4 mg IV was used as rescue antiemetic.²⁶

Our study was in accordance with Bakri et al who conducted a randomized, controlled, double blind study in which 86 adult patients scheduled for laparoscopic cholecystectomy were randomly divided into two groups. One group received single dose 1 mcg kg -1 of dexmedetomidine (Dexmed group) and other group received 8 mg dexamethasone (Dexa group) before skin incision. Incidence and severity of PONV were assessed during first 24 hours. Consumption of antiemetic was calculated during first 24 hours after surgery. It was found that 21% of the patients developed PONV in Dexmed group while in Dexa group 28% of the patients developed PONV (p=0.6). Severity of PONV was same between both groups (p=0.07). So, it was concluded that dexmedetomidine decreases the incidence and severity of PONV same as dexamethasone.²

Ye et al (2021) conducted a prospective, randomized, double-blind study to investigate the optimal dose of dexmedetomidine to maintain hemodynamic stability, prevent of cough and minimize postoperative pain for patients undergoing laparoscopic cholecystectomy. One hundred and twenty patients were randomly divided into D1, D2, D3 and NS groups in which dexmedetomidine 0.4, 0.6, 0.8µ/kg and normal saline were administrated respectively. PONV was recorded at 20 min(t1), 2h(t2), 6h(t3), 12h(t4), 24h(t5) and 48h(t6). The incidence of PONV in NS, D1, D2, D3 groups were 53.33, 50, 46.67, 40 % respectively with no statistically  significant differences among four groups. At t4(24h), the incidence of PONV in D2 and D3 group was less significantly than NS group (p=0.033).  The incidence of PONV could be significantly reduced by dexmedetomidine 0.6µ/kg or 0.8µ/kg (p<0.05). The study had similar results to our study.

The lower incidence of PONV in dexmedetomidine group is possibly related to the reduced consumption of intra-operative and postoperative opioids and inhalational agents. Also, dexmedetomidine decreases nor adrenergic activity after binding to alpha-2 presynaptic inhibitory adreno-receptors in locus coeruleus, which may result in antiemetic effect. Overall reduction in sympathetic outflow and catecholamine release caused by dexmedetomidine may also be related to low incidence of PONV.^1,2 Its antiemetic effect may be explained by direct antiemetic properties of α2 agonists. Opioid sparing effect of dexmedetomidine has been reported by many investigators. The precise mechanism for antiemetic effect of dexamethasone is still unknown. A common theory is antagonism of prostaglandin, but it may also inhibit the formation and release of 5- HT by depleting tryptophan or by preventing the activation of its receptors. 3 The dexamethasone is not beneficial in postoperative pain.

Demographic profile of the patients i.e age, gender distribution, weight distribution and ASA physical status of the patients were found comparable in both groups.  Duration of surgery and anaesthesia was found to be comparable to each other.  Baseline HR, SBP and DBP were comparable in both the groups. Fall in HR, SBP and DBP was not found to be statistically significant between two groups. The postoperative pain was significantly reduced in group A than group B at 10, 20 and 30 minutes after the surgery. However, VAS pain score was comparable between two groups at 40 minutes. Patients were found to be significantly more sedated after surgery in group A at 10,20 and 30 minutes than group B. All patients in both the groups responded readily to the name spoken at 40 minutes (MOAA/S score – 5). The incidence of post operative nausea and vomiting was found to be statistically comparable between two groups except at 12h after the surgery. The patients who received dexmedetomidine reported no incidence of PONV after 12 and 24 hours of surgery while 11.4% and 8.6% of patients who received dexamethasone experienced nausea and vomiting.  The severity of post operative nausea and vomiting was found to statistically comparable between two groups except at 6h after the surgery. Patients who received dexamethasone experienced more severe PONV at 6 h after the surgery than who received dexmedetomidine. One patient in group A had hypotension which was treated with injection mephentermine. No patient in any group had any episode of severe bradycardia or any dysrythmias.

After studying various factors, we conclude that dexmedetomidine 1 µg/kg given intravenously over 10 minutes after induction of anaesthesia and before skin incision prevent the postoperative nausea and vomiting similar to the 8 mg dexamethasone given intravenously after induction and before skin incision in patients undergoing laparoscopic cholecystectomy under general anaesthesia. Dexmedetomidine is superior than dexamethasone in preventing PONV at 12 and 24 h of the surgery, decreasing the severity of PONV at 6 hours of the surgery, relieving early postoperative pain, maintaining the intraoperative hemodynamic stability and a smooth recovery from the anaesthesia.

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