Post operative Nausea and Vomiting (PONV) is the most unpleasant complication in the perioperative period. (1) Incidence of PONV has been reported to be in the range of 20 -30%(2) PONV increases Intra Ocular Pressure,Intra Cerebral Pressure, causes wound dehiscence, patient dissatisfaction and prolongs duration of stay in hospital (1).

There are three major components of vomit reflex – the emetic detectors, integrative mechanism and motor output. The main sensors of somatic stimuli are located in the muscular wall of the gut  (  mechano and chemoreceptors  activated by contraction and distension of the gut and noxious chemical stimuli respectively ) and the chemo-receptor trigger zone (CTZ). CTZ located in area prostrema, which is highly vascular and no blood-brain barrier exists here. Chemicals in blood and CSF can thus stimulate it.(2)

The emetic centre is diffusely located in lateral reticular formation of medulla and mediates vomiting responses through vagus, phrenic and spinal nerves of abdominal muscles, receives input from higher cortical centres, somatic structures and from cranial nerves including trigeminal nerve. (2)

Central structures involved in vomiting response are rich in dopaminergic , muscarinic, serotonergic, histaminic, neurokinin – 1 and opioid receptors. PONV is multifactorial , though  prevented, cannot always be completely eliminated. Anti -emetics are the main stay of treatment.(2)Antiemetic drugs  that are available  include  anticholinergic (scopolamine), dopamine anatgonists(promethazine, metoclopramide ),antihistaminics (diphenhydramine ), 5HT3 receptor antagonists ( ondansetron, granisetron ) and steroids( dexamethasone).(3)

 Inspite of availability, no single agent is 100% effective, (3) and combination therapy may be needed to control PONV successfully.

PONV is a very common complication after middle ear surgeries, with an incidence upto 80%, when no antiemetics are used (4). Etiology of PONV after middle ear surgeries is multifactorial. There are abundant 5-HT3 receptors present in the vicinity of trigimenal nerve and vestibular labyrinth; hence , 5HT3 receptor antagonists are efficacious in middle ear surgeries. Ondansetron , a 5HT3 anatgonist  provides significant reduction in early PONV. Dexamethasone may act by serotonin inhibition in the gut  through prostaglandin antagonism. It can significantly decrease the tissue inflammation and thus reduces the ascending impulse to the vomiting centre. (4) It has been used to mainly reduce late PONV.

Ondansetron plus dexamethasone has been successfully used to treat emesis refractory to ondansetron alone. (3)

It is recommended that the drugs with different mechanisms of action should be used in combination to optimize the efficacy. (4)Therefore , a combination of dexamethasone and ondansetron is considered the optimum choice for prevention of PONV after middle ear surgery and has been used as standard of care in our hospital. Clinical trials with a new class of drugs “neurokinin receptor antagonist (NK -1 )-  Gabapentin” has recently been used  in treatment of nausea and vomiting.   Though the actual mechanism by which it prevents nausea and vomiting remains a topic of debate, it is suggested that it is effective in treatment of PONV by mitigation of tachykinin neurotransmitter activity.( 5) It  may also act by reduction in calcium signalling in area prostrema, or reduction in perioperative inflammation – thus reducing ileus or by reducing perioperative opioid consumption.(6)

 The purpose of this study is to compare Gabapentin  with Dexamethasone-Ondansetron combination in the incidence , severity of PONV and duration of antiemetic activity in middle ear surgeries.

Review of literature

·       Panda NB et al in 2004 studied 100 patients undergoing tympanomastoidectomy under general anaesthesia who received antiemetic drug 30min before surgery. Group O (50 patients) received   IV  ondansetron 4mg and the other 50 (Group OD)received  IV  ondansetron 4mg plus  IV dexamethasone 8mg. Rescue antiemetic requirement was found to be significantly less (p<0.0)1 in Group OD.They concluded that the combination of ondansetron and dexamethasone decreased the incidence of PONV (28% in Group O versus 6% in Group OD)  and showed improved patient satisfaction significantly in the postoperative period.(7)

·       Ashwani kumar et al in 2013 studied on 320 patients undergoing laparoscopic cholecystectomy. They divided them into 4 groups of 80 each. Group 1 received placebo, Group 2 received IV ondansetron 4mg, Group 3 received IV dexamethasone 8mg and Group 4 received IV ondansetron 4mg plus IV dexamethasone 8mg. In Group 4,  10% of patients had  nausea and vomiting compared to 85% in the placebo group (Group 1), 35% in Ondansetron group (Group 2) and 30 % in dexamethasone group (Group 3). Rescue antiemetic was required in 55% patients of placebo group (group 1), 35% in ondansetron group (group 2) and 30 % in dexamethasone group (group 3). None of the patients in the combination group required rescue antiemetic. They found PONV to be multifactorial and different receptors were involved in its etiology. Thus, they concluded that the combination of ondansetron and dexamethasone, acting on different receptors to  be more effective than each drug alone for prevention of PONV. (3)

·       Sameer Desai et al in 2013 compared 120 patients undergoing middle ear surgeries scheduled to receive IV dexamethasone 8mg plus IV ondansetron 4mg or IV ramosteron 0.3mg.  Ramosetron is more potent and has longer duration of antiemetic activity than ondansetron, due to higher binding affinity and slower rate of dissociation from the receptor. However, they found that patients in the group with ondansetron plus dexamethasone had significantly complete response (patients who never developed  nausea  or vomiting) in early postoperative period (2 to 24hrs - 76% vs 56%,  p = 0.02) and  late postoperative period (24 to 48hrs  -93%  vs 81% , p = 0.05). They concluded that  combination of dexamethasone plus ondansetron was superior to ramosteron .(4)

·       Morteza  Heidon et al in 2015 enrolled 90 patients undergoing middle ear surgeries and divided them into 3 groups of 30 each . Group 1 received IV granisetron 3mg 2 min before induction of anesthesia, group 2  received oral gabapentin 300mg 1 hour before anesthesia and group 3 received placebo. The incidence of PONV in group1 and 2 was significantly lower when compared with group3 (p<0.05). They concluded that gabapentin and granisetron have equal antiemetic effects. (1)

·       Neha Agarwal et al in 2015 studied the effects of oral gabapentin (400mg) and IV dexamethasone (8mg) given together or separately 1 hour before start of surgery. They studied on intraoperative hemodynamics, postoperative analgesia and PONV in patients undergoing gynecological procedure in 138 patients. They concluded that the combination of oral gabapentin and IV dexamethasone had significantly less hemodynamic changes , better post operative analgesia and less incidence of PONV than individual administration of each drug (p<0.001). (5)

Informed  consent of those who will undergo middle ear surgery under general anaesthesia will be taken.  The subjects will be randomized via computer generated table and allocated to one of the 2 groups  - Group G and Group DO.  Routine preoperative evaluation will be done. All the subjects will be informed about the score for PONV , VAS for pain on the previous day. As a standard practice, they will be kept fasting for 6 hours and  premedicated with Tab. Alprazolam 0.5 mg and Tab. Pantoprazole 40 mg on the night prior to surgery and on the morning of surgery. 

Group DO – Subjects will receive IV dexamethasone (100mcg/kg) at induction and  IV ondansetron (100mcg/kg)  before end of surgery.

Group G – Subjects will receive tab 300mg gabapentin per orally 1 hour with sips of water before the induction of anesthesia in preop room.

Intraoperatively standard  monitoring  is done by  electrocardiography, non-invasive blood pressure and pulse oximetry. A venous access (20G) will be secured under aseptic conditions. Intravenous fluid will be started and  0.2 mg of glycopyrrolate and 1 mg of midazolam will be given.

Standard anesthetic technique will be performed in these subjects. Preoxygenation with 100% O2 will be done for 3min  with a face mask.

Induction of anesthesia : IV fentanyl 2mcg/kg +IV propofol 1.5 to 2 mg/kg will be given followed by neuromuscular blocking agent IV atracurium 0.5mg/kg . At 3min, airway is secured with appropriate sized endotracheal tube.

Maintenance of anesthesia is with O2:Air (50:50), inhalational agent (isoflurane 0.8-1%  titrated to  keep MAC values between 1.0 to 1.4)  and IV atracurium 0.1mg/kg in divided doses. IV morphine 0.1mg/kg will be given for analgesia.

Post-surgery, the neuromuscular blockade will be reversed with IV neostigmine 0.5mg/kg and IV  glycopyrrolate 0.01mg/kg. Patients will be extubated and shifted to the recovery room.

The following parameters will be monitored and recorded

1.     The incidence of PONV in the postoperative period

  a.     Early PONV at 0 min, 15 min, 30 min, 1 hr, 2 hr

  b.      Late PONV at 4 hr, 6hr, 12hr, 18hr and 24hr.

2.     Severity of PONV. Scored as;

  0 = no nausea and vomiting

  1 = mild nausea not requiring treatment

  2 = moderate nausea, mild vomiting and requiring treatment

  3 = severe vomiting (2)

3. Duration of antiemetic effect: From the immediate postoperative period to the first time of occurrence of PONV.

4. Number of rescue antiemetic doses

5. Postoperative pain scores according to Visual Analogue scale (VAS)  scales at  0 min, 15 min, 30 min, 1 hr, 2 hr , 4 hr, 6hr, 12hr, 18hr and 24hr.

6. Incidence of postoperative sedation according to Ramsay sedation scale

Rescue antiemetic is IM Prochloperazine 5mg when PONV >2

Rescue analgesics with IV paracetamol 1gm when VAS >3 and tramadol 1mg/kg when VAS>6

Data collected will be tabulated in excel sheet and statistically analysed.