Primary outcomes

Major morbidity/mortality related to haemodynamic changes which follow tracheal intubation. As the majority of these changes settle within 5‐10 minutes, only morbidity/mortality occurring during this period or as a direct consequence of these changes will be included.
Examples of major morbidity:
Electrocardiographic evidence of intra operative ischemia following intubation leading to myocardial infarction subsequently ( evidence of raised creatinine phosphokinase MB fraction or troponin T ).
Rupture of aneurysm.
Acute cerebral haemorrhage.
Sudden deterioration in cardiovascular status or neurological status leading to prolongation of operating room/recovery room stay or admission to critical area.

Data will be collected as number of patients who had mortality or morbidity.

Secondary outcomes

1. Dysrhythmias. Studies recording any cardiac dysrhythmia during or following intubation will be included. Data will be collected as number of patients who had a dysrhythmia during the above period.

2. Studies observing ECG evidence of ischaemia. Data will be collected as number of patients who had ECG evidence of ischaemia, ST segment depression of more than 1 mm on ECG during or as a consequence of tracheal intubation.

Appropriate methods:
The data will be looked at qualitatively. Quantitative estimates of treatment effect will be performed if there will be meaningful number of studies.

Inclusion criteria

Randomized controlled trials on adult patients of either sex and any race, age above 18 years undergoing elective surgery who receive a pharmacological intervention before or at induction of anaesthesia to prevent the haemodynamic response related to tracheal intubation will be included.

Exclusion criteria

RCTs involving patients in whom tracheal intubation is performed in other settings e.g., ICU or accident and emergency unit, or those undergoing emergency surgery will not be included.

Selection bias

This will be determined as follows:

• • Adequate concealment. If allocation was through a central office or pharmacy controlled; pre‐numbered or coded identical syringes; on‐site computer systems with allocation kept in a locked unreadable computer file; or numbered, sealed opaque envelopes.

  • Inadequate concealment will be alternation using date of birth, open list of random numbers, day of week, or if a study only states that a list of number, table or envelopes were used

  • Unclear. If study does not report any concealment approach

  • Concealment not used

Also it will be observed whether inclusion and exclusion criteria were clearly defined in the text.

Performance bias

Blinding will be assessed as follows:

• • Patient not aware of treatment

  • Care provider not aware of assigned treatment

  • Persons responsible for assessing outcome unaware of assigned intervention (double blind)

  • Persons responsible for analysing data unaware (triple blind)

Only double and triple blinding will be taken as blinding criteria being met

Attrition bias

Any loss of participants from study after allocation will be noted e.g. withdrawal, dropouts or protocol deviation

Detection bias

This would be gauged from the following:

• • Outcome measures clearly defined in text

  • Outcome assessors were blinded to the allocation of patients

  • Timing of measurement to outcome was appropriate

Based on selection bias, the validity will be rated by the reviewers as:

• • Low risk of bias, if majority of the above criteria are met ( more than 75% criteria met)

  • Moderate risk of bias, if criteria are partially met (50‐75% criteria met )

  • High risk of bias, if majority of the above criteria are not met ( more than 50% criteria not met )

Further information from the authors will be obtained where possible; where it is unclear whether criteria was met or not in case of concealment and blinding.

Any disagreement between the two reviewers will be referred to a third identified reviewer. The reviewer will fill a separate data abstraction form, which will be flagged.

Participants

The following will be noted:

• • Number of patients enrolled in the study and number of patients in each treatment group

  • Mean age and age range

  • Sex of patients

  • Definition of high risk in the study setting: Pre‐existing hypertension (code 1) . Pre‐existing ischemic heart disease (code 2). Pre‐existing cerebral pathology; cerebral aneurysm present (code 3), history of cerebrovascular accident with full neurological recovery (code 4), previous history of stroke or cerebrovascular accident with partial neurological recovery (code 5). Raised intracranial pressure (code 6).

  • Pre‐existing aortic aneurysm (code 7)

  • Any others (code 8)

Interventions

The following will be noted:

• • Induction agent used; Thiopentone, Propofol, Ketamine, Midazolam, Inhalational agents, more than one agent used

  • Pharmacological class of interventions; Narcotics (code 1), Local anaesthetics (code 2), Peripheral vasodilators (code 3), Sympathetic blockers (code 4), Centrally acting adrenergic agonists (code 5), Miscellaneous (code 6)

  • Route of intervention; Intravenous (code 1), Bolus (code 1B), Infusion (code 1i) , Oral (code 2), Inhaler (code 4), Spray (code 5)

  • Control Group; Placebo, Drug intervention

  • Drug dose of interventions in mg kg‐1 or microgram kg‐1

  • Adverse effect of study drugs seen

  • Any drug delivery changes in response to changing haemodynamics