European Journal of Cardiovascular Medicine

Postoperative sore throat is one of the most undesirable postoperative complaints after general anaesthesia. Incidences range from 14.4% to 50% after endotracheal intubation.1 This complication is most distressing to the patient and unfortunately is also the most overlooked postoperative complaint. But it may in fact negatively impact the patients’ quality of life.2,3,4

General anaesthesia combined with endotracheal intubation and controlled ventilation is the most common form of anaesthesia technique applied for different surgical specialties5 Endotracheal tubes allow pressure to be maintained in the airways during mechanical ventilation and prevent aspiration of regurgitated gastro oesophageal contents. However, the pressure of the ETT cuff is transmitted to the tracheal mucosa, which when elevated might cause ischemia of the mucosal vessels followed by serious complications such as ciliary loss, inflammation, ulceration and haemorrhage. The idea of using cuffed endotracheal tube is to achieve a seal between the cuff and the trachea with a pressure sufficient enough to prevent aspiration but not so much that tracheal blood flow is impeded. An acceptable cuff pressure ranges from 20 to 30 cm H2O6

This pressure limit is determined in part by capillary blood pressure supplying the trachea, which is approximately 30 cms H2O and the minimum occlusive intra-cuff pressure required for positive pressure ventilation, to prevent aspiration, i.e., approximately 20 cm H2O 6,7 Thus, there is a narrow range of cuff pressures required to maintain a functionally safe seal without exceeding capillary blood pressure.5.  Elevated ETT cuff pressure greater than the capillary pressure of the tracheal artery i.e.30cms of water can cause tracheal ischemia proportional to the pressure exerted by the cuff and to the duration of exposure. It is therefore recommended to maintain the cuff pressure between 20 and 30 cms of water. Over inflation of the cuff may lead to ischemia, inflammation, ulceration, granulation and stenosis at the contact site between the cuff and the tracheal wall 8,9 Moreover, postoperative sore throat is commoner in cases in which the endotracheal cuff pressure is elevated 9,10. Also, this low risk complication can have legal implications11. On the other end of the spectrum, patients can be at risk of aspiration if the cuff pressure is too low (<20 cm H2O). 5.   

The occurrence of sore throat, cough, and hoarseness post extubation is common and are collectively known as the post extubation syndrome.12. An array of various techniques have been employed  over the years to decrease the incidence of postoperative sore throat namely, non-pharmacological methods like usage of smaller sized endotracheal tubes, minimising intracuff pressure, lubrication with water soluble jelly, gentle airway instrumentation and avoiding suctioning and also pharmacological methods like using Lignocaine, Benzydamine hydrochloride, Beclomethasone, Betamethasone and Ketamine.

We hypothesised that intracuff Tramadol may be effective in reducing postoperative sore throat through its NMDA receptor antagonistic activity and local anaesthetic effect. When Tramadol is injected into the endotracheal tube cuff, it diffuses through the semi permeable membrane wall and induces its action in the trachea. This increases airway tolerance to tracheal tube. After tracheal extubation, the incidence of coughing may be reduced, thus minimising haemodynamic alterations.

AIMS AND OBJECTIVES

To compare the effects of intracuff tramadol 2mg/kg versus intracuff air on postoperative sore throat in patients undergoing elective surgery under general anaesthesia with endotracheal intubation

Study Setting and Source:

This study was performed at Sri Ramachandra Hospital after obtaining university ethical committee approval and an informed consent from all the patients. Patients posted for elective surgeries under general anaesthesia with endotracheal intubation who satisfied the inclusion criteria were included in the study.

Sample size: Using open EPI software with a power of 80%, an alpha error of 1 % and a confidence interval of 99%, we arrived at a total sample size of 96 patients with 48 in each group.  

Study Method: Patients were randomized into two groups using sealed envelope technique.

Group A – Intra-cuff Tramadol 2mg/Kg, Group B – Intra-cuff Air 

Inclusion Criteria:

• 18-60 years of age.
• Both the genders.
• American Society of Anaesthesiologists (ASA) 1 and 2 patients.
• Elective surgeries in supine position under general anaesthesia using endotracheal tube intubation, with an anticipated duration of surgery<240minutes(4 hours).

Exclusion Criteria:

• Patient refusal.
• Patients who are allergic to Tramadol.
• ASA 3, 4 and 5 patients.
• Obese patients.
• Pregnant patients.
• Patients with H/O smoking.
• Upper respiratory tract infection/laryngitis/ pharyngitis.
• Emergency surgeries/surgeries in prone position/ use of flexometallic tube
• Head and neck surgeries.
• Anticipated duration of surgery >240 minutes (4hours).

Study Protocol:

Patient’s complete history was elicited and a thorough physical examination was done during preoperative assessment the day before surgery. Baseline Investigations were noted down. A written informed consent was obtained from the patient. Patient was kept NPO -8 hours for solids and 2 hours for clear liquids. No premedication was given to the patient.  

Procedure 

After shifting the patient to the operating room, standard baseline monitors were connected, baseline vitals were noted & IV access obtained. Patients were randomly allocated into two groups by drawing lots labelled “A” and “B” and their hospital numbers were documented on the lot assigned. The lots were retrospectively used to find out the group to which the patient was allocated.

Pre oxygenation was done with 6 litres of 100% oxygen for 3min through face mask. Endotracheal tube cuff was thoroughly checked for any leaks.

Induction was done with Inj. Fentanyl 2mcg/kg, Propofol 2mg/kg, Vecuronium  0.1mg/kg I.V and Sevoflurane. Laryngoscopy was done using McIntosh blade. Patient was intubated using 7mm endotracheal tube for females and 8mm endotracheal tube for males.

Patients were randomly allocated into two groups by drawing lots labelled A and B and their hospital numbers were documented on the lot assigned. The lots were retrospectively used to find out the group to which the patient was allocated.

GROUP A: Endotracheal tube cuff was inflated with Tramadol 2mg/kg and saline was added as required until an intracuff pressure of 20 cms of water was achieved in the cuff pressure manometer.5 minutes time was given for equilibration.

GROUP B: Cuff was inflated with air until a pressure of 20cms of water was achieved in the cuff pressure manometer.5 minute’s time was given for equilibration.

Volume of Tramadol and air required to achieve an intracuff pressure of 20cms of water was noted down.

Anaesthesia was maintained with Sevoflurane in air and oxygen and with vecuronium as required. Haemodynamic parameters like HR, BP, MBP and SpO2 were noted down every 15 minutes. At the end of surgery, intracuff pressure was noted down using a cuff pressure manometer. Reversal of neuromuscular blockade was done using Inj.Neostigmine 0.05mg/kg and Inj, Glycopyrrolate 0.01mg/kg I.V. Intracuff volume was noted down while deflation. Extubation was done after thorough suctioning.

Cough if any, immediate post extubation was noted down and graded.

0 – No cough

1 – Cough lasting for<15 seconds.

2 – Cough lasting for >15 seconds.  

Parameters Assessed Postoperatively:

At the 1st hour, 6 hours and 24 hours post-surgery. 

Primary Outcome:

 To assess the incidence and severity of postoperative sore throat at 1 hour, 6 hours and 24 hours post-surgery.

Sore Throat:

0 – No sore throat

1 – Minimal sore throat (lesser than that associated with common    cold)

2 – Moderate sore throat (equal to that associated with common    cold)

3 – Severe sore throat (more than that associated with common    cold)   

Secondary Outcome:

To assess coughing, hoarseness of voice and dysphonia if any at 1 hour,6 hours and 24 hours post-surgery.

Cough:

0 – No cough

1 - Minimal cough

2 – Moderate cough

3 - Severe       

Hoarseness of Voice:

 0 – No hoarseness at any time since the surgery.

 1 – No hoarseness at the time of interview.

 2 – Hoarseness at the time of interview noted by patient only.

 3 – Hoarseness easily noted at the time of interview. 

Dysphonia       Yes/No

Mean Arterial Pressure:

There was no significant variation in the mean arterial pressure between group A and B right from the 0th minute to 1 hour.

Cuff Volume:

There was a significant difference in the cuff volume at the start of surgery and end of surgery between the 2 groups.

Cuff Pressure:

There was a significant difference in the cuff pressure at the start of surgery and end of surgery between the 2 groups.

Duration of Surgery:

There was no significant difference in the duration of surgery among the 2 groups.

Cough Immediate Post Extubation:

There was a highly statistically significant difference between the groups pertaining to cough immediate post extubation. 19 patients (39.6%) in the air group had cough immediate extubation lasting for less than 15 seconds whereas none of the patients in the tramadol group had cough immediate post extubation.

Sore Throat:

There was a significant difference in the presence of sore throat at the 1st hour post-surgery. Only 3 patients (6.3%) out of 48 in the tramadol group had minimal sore throat in the 1st hour whereas 35 patients (72.9%) had minimal sore throat and 9 patients (18.8%) had moderate sore throat in the air group.

In the same way, at the 6th hour post-surgery, there was a significant difference in sore throat. Only a single patient had sore throat and that too minimal in the tramadol group whereas 25 patients had minimal sore throat and 1 patient had moderate sore throat in the air group

      At 24 hours post-surgery, there was no difference in sore throat among the 2 groups

At 24 hours post-surgery, there was no difference in sore throat among the 2 groups

Cough:

At the 1st hour post-surgery, there was a significant difference between the 2 groups with regards to cough. None of the patients in the tramadol group had cough whereas 18 patients had minimal cough and 3 patients had moderate cough in the air group.But at the 6th hour and 24 hours post-surgery, there was no significant difference in cough among the 2 groups

Hoarseness:

There was a significant difference in the presence of hoarseness at the 1st hour and 6 hours post-surgery between the groups. None of the patients had hoarseness in the tramadol group in either the 1st hour or 6 hours post-surgery whereas in the air group,14 patients had grade1 hoarseness and 6 patients had grade 2 hoarseness in the 1st hour and 7 patients had grade 1 hoarseness and 3 had grade 2 hoarseness in the 6th hour. At 24 hours post-surgery, there was no difference between the 2 groups.

Dysphonia:

There was a significant difference among the 2 groups pertaining to the presence of dysphonia in the 1st hour post-surgery. 12 patients (25%) had dysphonia in the air group whereas none of the patients in the tramadol group had dysphonia. At the 6th hour and 24 hours post-surgery, none of the patients, neither in the air nor tramadol group had dysphonia.

Postoperative sore throat is one of the most common and agonising complaints after endotracheal intubation. Waters and Guedel in 1928 introduced the cuffed endotracheal tubes. The cuff of the endotracheal tube serves important functions like protecting the respiratory tract against aspiration by providing an airtight seal against gas leak and allowing adequate positive pressure ventilation.

Amongst the sequelae inherent to the usage of endotracheal tube are local irritation and inflammation of the airway caused by prolonged inflation of the cuff resulting in post intubation morbidities like sore throat, hoarseness of voice and cough.

Coughing during emergence from general anaesthesia can result in hypertension, tachycardia, tachyarrhythmias increased intraocular and intracranial pressures, myocardial ischemia, bronchospasm and surgical bleeding. Rapidly adapting stretch receptors in the tracheal mucosa are believed to be the irritant receptors meant for cough. These receptors are highly sensitive to mechanical stimuli like displacement and stretch.

Any technique that would allow patients emerging from anaesthesia to tolerate an endotracheal tube while affording airway protection with intact supraglottic reflexes would be desirable.

Several drugs have been used to reduce POST over the years like Lignocaine, Benzydamine hydrochloride, Beclomethasone, Betamethasone, Dexamethasone, Ketamine etc.

Ours is a novel study in which we instilled tramadol hydrochloride into the endotracheal tube cuff in-order to reduce postoperative sore throat, coughing, hoarseness and dysphonia.

It has been found that NMDA receptor antagonists when peripherally administered have analgesic and anti-inflammatory effects.

We hypothesised that inflating the endotracheal tube cuff with tramadol rather than air can reduce the incidence of cough during extubation and postoperative sore throat. Tramadol placed in the endotracheal cuff might diffuse across the cuff membrane. The cuff could act as a reservoir for tramadol or local anaesthetics allowing diffusion and subsequent anaesthesia of the underlying mucosa. Although there are several invitro studies to demonstrate the diffusion of intracuff lignocaine through the endotracheal tube cuff, there are none on intracuff tramadol. Hence we did an invitro study in which we inflated the endotracheal tube cuff with methylene blue infused tramadol. We then placed the tube in a bowl filled with normal saline. We found that within an hour of inflating, the methylene blue infused tramadol had diffused through the cuff and stained the surrounding normal saline in the bowl. This showed that tramadol could diffuse through the cuff of the polyvinylchloride tube.

Our study showed that intra-cuff tramadol was highly effective in reducing the incidence and severity of postoperative sore throat when compared to the air group after endotracheal intubation in patients undergoing elective surgeries. Also cough, hoarseness and dysphonia were significantly lower in the intra-cuff tramadol group when compared to the air group.

Cough Immediate Post Extubation:

There was a highly statistically significant difference between the groups pertaining to cough immediate post extubation. 19 patients (39.6%) in the air group had cough immediate extubation lasting for less than 15 seconds whereas none of the patients in the tramadol group had cough immediate post extubation. The findings of our study were similar to that of the study done by Estebe et al in which they observed less cough and restlessness in the group that received alkalinised intracuff lignocaine(5%) when compared to that of the air group(95%). Bousselmi et al found that the incidence of coughing and bucking was 20% in the lidocaine group when compared to 80% in saline group.  Fagan et al conducted a study in which they observed a lower incidence of coughing (16%) in the intracuff lignocaine group when compared to the air(38%) or saline group(44%). Navarro, Lima et al found that 75% of patients in the saline group had coughing at emergence whereas only 25% had in the lignocaine group.

Sore Throat:

In our study, there was a significant difference in the presence of sore throat at the 1st hour and 6 hours post-surgery. Only 3 patients (6.3%) out of 48 in the tramadol group had minimal sore throat in the 1st hour whereas 35 patients (72.9%) had minimal sore throat and 9 patients (18.8%) had moderate sore throat in the air group. In the same way, at the 6th hour post-surgery, there was a significant difference in sore throat. Only a single patient (2.1%) had sore throat and that too minimal in the tramadol group whereas 25 patients (52.1%) had minimal sore throat and 1 patient (2.1%) had moderate sore throat in the air group. This highly positive result was unexpected and might be related with the combination of two factors such as use of intracuff tramadol as well as maintenance of lower intracuff pressures.

At 24 hours post-surgery, there was no difference in sore throat among the 2 groups. Our findings were consistent with that of two separate studies done by Estebe et al. They noticed that sore throat was decreased significantly in the intracuff lignocaine group when compared to the air group but only during the two postoperative hours. This might be due to the fact that they inflated the endotracheal tube cuff to obtain the minimal occlusive volume rather than guided by the cuff pressure manometer. The cuff pressure was checked just once at the beginning of surgery although Nitrous oxide was used in their surgeries. Nitrous oxide diffuses into the cuff more rapidly than it diffuses out because of the partial pressure gradient across the PVC membrane and increases the cuff pressure. Also, sore throat was analysed using Visual analog scale.

Navarro, Lima et al also observed a significant reduction in post-operative sore throat in the intracuff lignocaine group when compared with the saline group (20%) at 6 hours post surgery. It is to be noted that similar to the findings of our study, there was no difference in sore throat between the two groups at 24 hours post-surgery. In a study done by Jaichandran13 et al, they found that the incidence of sore throat was found to be lower in both the liquid groups i.e intracuff alkalinised lignocaine (12%) and saline group(25%) when compared to the air group(75%) both in the 1st hour and 24 hours post surgery..  This is in good agreement with the observations of Bousselmi et al who found that the incidence of sore throat was 20% in the lidocaine group when compared to 80% in the saline group in the 1st hour post surgery. At 24 hours post surgery there was no significant difference.

However, Navarro14, Braz et al found that though the incidence of sore throat was greater in air group(16%), there wasn’t a significant difference between the two groups(5% in the lignocaine group). The intensity of sore throat also revealed little difference. Although this study also used nitrous oxide like the previous studies, the cuff pressure was maintained at a lower  level of 20cms of water. This might be the reason for such results.  Similarly, Shroff et al found higher incidences of sore throat in the air group(39%) when compared to the saline(20%) and lignocaine group(18%).

Post Operative Cough:

At the 1st hour post surgery, there was a significant difference between the 2 groups with regards to cough. None of the patients in the tramadol group had cough whereas 18 patients (37.5%) had minimal cough and 3 patients (6.3%) had moderate cough in the air group. But at the 6th hour and 24 hours post surgery, there was no significant difference in cough among the 2 groups.

These findings were similar to the observations made by Estebe16 et al in the study they did in 2004. Navarro, Lima et al also found that the incidence of coughing was considerably lower in the lignocaine group when compared to the saline group. In a study done by Shroff et al , they noticed that coughing was more in the air group when compared to the liquid groups.

Hoarseness:

There was a significant difference in the presence of hoarseness at the 1st hour and 6 hours post surgery between the groups. None of the patients had hoarseness in the tramadol group in either the 1st hour or 6 hours post surgery whereas in the air group,14 patients(29.2%) had grade1 hoarseness and 6 patients(12.5%) had grade 2 hoarseness in the 1st hour and 7 patients(14.6%) had grade 1 hoarseness and 3 (6.3%)had grade 2 hoarseness in the 6th hour. At 24 hours post surgery, there was no difference between the 2 groups.Our findings were consistent with those of Estebe16 et al who noted that hoarseness and was more in the air group (80%) than in the liquid groups (10%).  Navarro13, Lima et al found no significant differences in the incidence of hoarseness within the two groups (5%).This might be due to the fact that both the groups used in their study were liquid groups. Navarro, Braz et al also found no differences in the incidence of hoarseness between the air and lignocaine groups (40% in air group and 35% in the lignocaine group).This might be due to the fact that the intracuff pressure was maintained at a lower limit of 20cms of water. On the contrary, Shroff et al found that the incidence of hoarseness was more in the air group (39%) when compared to the saline (24%) or lignocaine group (16%).

Dysphonia:

There was a significant difference among the 2 groups pertaining to the presence of dysphonia in the 1st hour post surgery. 12 patients (25%) had dysphonia in the air group whereas none of the patients in the tramadol group had dysphonia. At the 6th hour and 24 hours post surgery, none of the patients, neither in the air nor tramadol group had dysphonia. Estebe16 et al also found that the incidence of dysphonia was more in the air group (35%) than in the liquid groups. Bousselmi15 et al found no difference at all between the two groups pertaining to dysphonia. Incidence was 5% in both the groups. Though several studies have used intracuff Lignocaine and observed similar beneficial effects, there is always the fear of lignocaine toxicity. Also, in the event of a cuff rupture, a relatively high dose of lignocaine can be delivered into the trachea and bronchus leading to toxicity. Hence blood concentrations of lignocaine are to be monitored for safe practice which might prove cumbersome and there is also the matter of cost and it might also be time consuming.

Nitrous oxide easily diffuses inside the endotracheal tube cuff, thereby increasing their pressures. Overinflation of the cuff and the consequent tracheal mucosa lesions result in sore throat, hoarseness, coughing and restlessness, thus causing discomfort to patients post extubation. Hence we used air instead of nitrous oxide in our study. Using these tramadol instilled cuffs for longer duration surgeries would result in better outcome as diffusion across the cuff membrane is a function of time. All cuffs of the endotracheal tubes used were intact post extubation. Since liquid media are used in laser surgeries, intracuff tramadol could be used instead of saline since it promises added benefits. Since our study showed statistically and clinically significant decrease in cough and smoother emergence with use of intracuff tramadol, it can be used safely in ophthalmic and neurosurgical procedures without the fear of increase in intraocular or intracranial pressures. Also, inflating the cuff with tramadol might be beneficial in cardiovascular surgeries and in patients with ischemic heart diseases. This might also prove to be useful in patients requiring prolonged intubation and /or mechanical ventilation to improve tube tolerance and reduce sore throat. This might reduce the sedation and analgesia requirements in such critically ill patients, thereby reducing the length of hospital stay, morbidity and mortality.

Based on our study, we conclude that intracuff tramadol used in doses of 2mg/kg significantly reduces postoperative sore throat in the 1st hour and 6 hours post-surgery. It is also found to significantly reduce the cough immediate post extubation providing smoother emergence as well as postoperative cough and hoarseness in the 1st hour and 6 hours post-surgery.

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