synopsis

EFFICACY OF INTRAVENOUS LIDOCAINE IN PREVENTING FENTANYL-INDUCED COUGH BEFORE INDUCTION OF ANAESTHESIA: A RANDOMISED CONTROLLED TRIAL

SYNOPSIS OF THE STUDY ENVISAGED FOR THE THESIS FOR THE DEGREE OF DOCTOR OF THE MEDICINE, ANAESTHESIOLOGY

BY:DR. PRALAY SHANKAR GHOSH

DEPARTMENT OF ANAESTHESIOLOGYNORTH BENGAL MEDICAL COLLEGE AND HOSPITAL

P.O.-SUSHRUTANAGARDIST: DARJEELING

SESSION: 2010-2013

UNDER THE GUIDENCE OF:PROFESSOR (DR.) SEKHAR RANJAN BASU

PROFESSOR & HEADDEPARTMENT OF ANAESTHESIOLOGY

NORTH BENGAL MEDICAL COLLEGE AND HOSPITAL

AND CO-GUIDENCE OF:DR. GOUTAM CHOUDHURIASSOCIATE PROFESSOR

DEPARTMENT OF ANAESTHESIOLOGYNORTH BENGAL MEDICAL COLLEGE AND HOSPITAL

UNDER THE WEST BENGAL UNIVERSITY OF HEALTH SCIENCESSALT LAKE, KOLKATA, INDIA


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Introduction:

Fentanyl citrate is a synthetic narcotic analgesic. It induces intense analgesia with a rapid onset, short duration of action, minimal cardiovascular depression and minimal histamine release (due to the citrate in fentanyl citrate). It has high potency and a short half-life and thus is a reasonably good agent to suppress the haemodynamic perturbations associated with the laryngoscopy and intubation in patients undergoing surgery1. It is widely used during induction of general anaesthesia and in the perioperative period.

But one of its important side effect is cough2. This tussive effect may be of concern specially in patients with increased intracranial pressure, open eye injury or increased intraabdominal pressure3.

Mechanism of this cough is inhibition of central sympathetic outflow causing vagal predominance, resulting in cough and reflex bronchoconstriction. Pulmonary chemoreflex stimulation and histamine release are the other possible mechanisms.

Different studies have shown the incidence of such cough to be 28-65% in Asiatic population, after intravenous injection of fentanyl in doses ranging from 2-5 mcg/kg .given over 1-5 seconds.4

Different techniques and drug therapy have been employed to reduce the cough with varying degree of success. Uses of ketamine, clonidine or dexamethasone before fentanyl injection have been found to be successful in various studies. Inhalational salbutamol3 reduces the cough incidence due to its beta adrenergic stimulatory effect over bronchial smooth muscle. Recent studies revealed role of pre-emptive injection of lower dose of fentanyl. Huffing maneuver, a forced expiration against closed glottis and slower injection rate have resulted in decreased cough incidence.

Lidocaine is a local anaesthetic agent with an amide group. Intravenous lidocaine was found to be effective in suppressing cough associated with endotracheal intubation and extubation5. In this study, we will try to investigate this property of intravenous lidocaine by injecting it before fentanyl injection to reduce the incidence of fentanyl-induced cough.

Though usually self-limited, fentanyl-induced cough may be life-threatening in patients with certain co-existing diseases6 and so the problem must be strictly dealt with by the attending anaesthesiologists. Previous study by Pandey CK et al. suggested risk reduction of 21.12% for fentanyl-induced coughing after pretreatment with IV lidocaine. Our study for that purpose will be carried out with this hypothesis that, the incidence of fentanyl-induced cough can be reduced by 30% using lidocaine intravenously before intravenous fentanyl prior to induction of general anaesthesia, by reducing the dose of fentanyl as well as the speed of injection.

Aims and objectives of the study:

This study will be carried out to determine the efficacy of intravenous lidocaine in patients undergoing elective surgery under general anaesthesia, compared to placebo, in respect to-

a) Reduction in the incidence of fentanyl-induced cough (primary outcome)b) Decrease in haemodynamic alterations during intubation (secondary outcome)c) Minimizing the adverse effects if any (secondary outcome)

Materials and methods:

1. Study area:

The study will be carried out on patients undergoing elective surgery under general anaesthesia. It will be conducted in the department of anaesthesiology of North Bengal Medical College to see the effect of intravenous lidocaine on the incidence of cough induced by fentanyl before induction of general anaesthesia. From the previous records, we are expecting at least 900 elective surgeries during the study period.

2. Study population:

Case definition- Adult patients of either age of ASA status I-II aged between 18-65 years, scheduled to undergo elective surgery.

Exclusion criteria:

1. Impaired kidney or liver functions2. A history of bronchial asthma and chronic obstructive pulmonary disease3. A history of smoking4. A history of chronic cough5. Respiratory tract infection6. Hypertensive patients on angiotensin converting enzyme inhibitors7. A hypersensitivity to local anaesthetics8. Seizure disorders

3. Study period:

The study will be started after getting permission from Hospital Ethical Committee and approval of West Bengal University of Health Sciences. It will span approximately one year from July 2011 to June 2012.

4. Sample size:

Sample size of the study is 44 in each group based on the following parameters1. α value 0.052. Power of the study 80%

As there is possibility of a dropout of 10%, 96 patients will be enrolled in the study.We are expecting a difference of at least 30% in reduction of cough from a previous study.

5. Sample design:

Patients will be randomly allocated into two equal groups (Group L and Group S)by computer generated block randomisation.

6. Study design:

Prospective randomised double blinded study. Here both the patients who will receive the drug and the person who will inject and observe the effect of the drug will be unaware of study protocol.

7. Parameters to be studied:

a) Severity of the cough, if present, in terms of mild (1-2), moderate (3-4) and severe (5 or >5) gradation.b) Haemodynamic stability in terms of heart rate, mean arterial pressure, SpO2 and EtCO2 changes at 0(at intubation), 3 and 5 minutes after intubation.c) Adverse effects- respiratory depression, bradycardia, convulsion etc.

8. Study tools:

a) Proforma of written informed consent and data collectionb) Anaesthetic machine and other necessary equipments for airway managementc) Tools of monitoring i.e. electrocardiogram, NIBP, pulse oxymeter, capnometer etc.d) Drugs- tab. diazepam, tab. ranitidine, inj. propofol inj. midazolam, inj. lidocaine, inj. fentanyl, inj. vecuronium inhalational isoflurane, inj. metoclopramidee) an emergency airway cart.

9. Study technique:

The study will be conducted after getting permission from Hospital Ethical Committee and approval of West Bengal University of Health sciences. Eligible patients will be included into the study considering both inclusion and exclusion criteria. Written informed consent will be obtained from all patients included in the study after proper discussion of the study procedure in their own languages at the preoperative visits. Patients will be randomly allocated to two groups, receiving either Inj. lidocaine (group L), or normal saline (group S).

Interventions:

Each patient will be advised to take tab. diazepam 5 mg, tab. ranitidine 300 mg on the night before surgery. The patient will be transferred to operation theatre on scheduled time and lactated ringers’ solution will be started through an intravenous line. Monitors will be attached to the patient and the baseline vital parameters will be measured. The patient will be then pre-medicated with Inj. ranitidine (50 mg) iv, inj. glycopyrrolate (0.2 mg) iv and inj. midazolam (2 mg) IV.

Both the drug and the placebo (normal saline) will be prepared in unlabelled 5cc syringes as colourless liquids and will be handed over to an anaesthesiologist who is unaware of the study protocol. He will inject the drugs while the patient will also be unaware, making the study double blind. Inj. lidocaine will be given intravenously in a dose of 1.5 mg/kg over 5 seconds one minute before injecting intravenous fentanyl 2µg/kg which will be injected over 10 seconds. The same person injecting the drugs will observe and grade cough (if any) accordingly. The period of observation will be 3 minutes and then, induction will be done with Inj. thiopentone (3-5mg/kg). the patient will then be intubated with inj. vecuronium. his /her vitals will again be recorded (at 0, 3 and 5 minutes after intubation) to see changes from the basal values. Any adverse effect, if occurs, will also be recorded and steps will be taken according to the severity.

10. Analysis of data:

Data will be analysed with appropriate statistical methods.

REVIEW OF LITERATURE:

1. In 1985, Yukioka H et al.5 in their study suggested the role of Inj. lidocaine to suppress the cough reflex alongwith with the mechanically-induced and chemically-induced airway reflexes.

2. Bohrer et al4. In 1990, suggested that fentanyl-induced cough may be due to stimulation of pulmonary chemoreflex and J receptors by fentanyl.

3.In 1992, Gin and Chui et al2. observed a young patient with acute extradural haematoma to have continuous coughing for five seconds after fentanyl injection during induction. The cough was suppressed by thiopentone.

4. In 1998, Ko SH et al.1 suggested use of fentanyl at a dose of 2 mcg/kg 5 minutes before intubation (time for peak analgesic effect) to haemodynamic responses to tracheal intubation.

5. In 2001, Tweed et al.6 suggested that coughing during induction of anaesthesia may increase intracranial pressure, intraperitoneal pressure and intraocular pressure. Such cough, when continuous, may require sedatives and muscle relaxants.

6. Agarwal A et al.3 in the year 2003 suggested role of lidocaine, ephedrine, beta-2 receptor agonist, ketamine and clonidine in suppressing fentanyl-induced cough due to the broncho-relaxant effect on airway smooth muscle.

REFERENCES:

1.Ko SH, Kim DC, Han YJ, Song HS. Small dose fentanyl: optimal time of injection for blunting the circulatory responses to tracheal intubation. Anesth Analg 1998;86:658-61.

2. Gin T, Chui PT. Coughing after fentanyl [letter]. Can J Anaesth 1992;39: 406.

3. Agarwal A, Azim A, Ambesh S, et al. Salbutamol, beclomethasone or sodium chromoglycate suppress coughing induced by iv fentanyl. Can J anesth 2003;50: 297-300.

4. H Bohrer, F Fleischer, P Werning, (1990). Tussive effect of a fentanyl bolus administered through a central venous catheter. Anaesthesia 1990;45: 18-21.

5. Yukioka H, Hyashi M, Yoshimoto N, et al. IV lidocaine as a suppressant of coughing during tracheal intubation. Anesth Analg 1985;64: 1189-92.

6. Tweed WA, Dakin D. Explosive coughing after fentanyl injection. Anesth Analg 2001;92:1442-3.


PATIENT ID: NAME-

REG. NO.- WARD- BED NO.-

DEMOGRAPHIC PROFILE: AGE- HEIGHT-

WEIGHT- ASA STATUS-

DURATION OF SURGERY:

SEVERITY OF COUGH:

NO COUGH MILD COUGH MODERATE COUGH

SEVERE COUGH

VITAL PARAMETERS:

PARAMETERS BASELINE

DURING AND AFTER INTUBATION0 MIN 3 MIN 5 MIN

MEAN ARTERIAL BPHRSpO2

ETCO2

INCIDENCE OF ADVERSE EFFECTS:

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