Cohort
Bozeman, William P. MD; Idris, Ahamed H. MDIntracranial Pressure Changes during Rapid Sequence Intubation: A Swine Model
Journal of Trauma
February 2005, pp 278-283
- Submitted by:Dale Ray - Emergency Medicine Faculty
- Institution:Grand Rapids MERC/ Michigan State University, Grand Rapids, MI
- Date submitted:14th July 2006
1
Objectives and hypotheses
1.1
Are the objectives of the study clearly stated?
To report the development of a model in pigs to measure intracranial pressure (ICP) during laryngoscopic intubation while using a variety of common emergency rapid sequence intubation (RSI) induction agents.
2
Design
2.1
Is the study design suitable for the objectives?
Yes, crossover trial design using an animal model
2.2
Who / what was studied?
Eight adult swine were instrumented with arterial and intracranial pressure monitors.
2.3
Was a control group used if appropriate?
No "control pigs" rather each pig received each RSI regimen and then compared with one another. The regimens were thiopental alone, thiopental + succinylcholine (1 mg/kg IV), thiopental + succinylcholine + lidocaine (1 mg/kg IV), and thiopental + succinylcholine + lidocaine + pancuronium (0.01 mg/kg).
2.4
Were outcomes defined at the start of the study?
The outcomes reported included mean arterial pressure, cerebral perfusion pressure, ICP during RSI of the swine model using each of these four regimens.
2.5
Was this the right sample to answer the objectives?
Yes, swine were chosen for this model because of low cost, size, and compatibility with standard equipment and available laboratory facilities. In addition, contrary to canines, swine have a laryngeal anatomy that is relatively difficult to orally intubate, making swine an excellent model for a study in which laryngeal manipulation is an important stimulus.
2.6
Is the study large enough to achieve its objectives? Have sample size estimates been performed?
No, 13/32 intubation attempts were discarded because of a priori study design issues (difficult intubation or malignant hyperthermia). Sample size estimates were not described.
2.7
Were all subjects accounted for?
Yes, all pigs were monitored in a similar fashion until all four regimens employed.
2.8
Were all appropriate outcomes considered?
ICP is a surrogate marker. The real outcome of importance to patients and clinicians is the neurological recovery. Additional surrogate markers for future study include cerebral oxygenation and metabolism, but ultimately researchers will need to assess the long term neurological recovery and functional independence of these animals (and ultimately patients).
2.9
Has ethical approval been obtained if appropriate?
Yes, approval of the institutional animal care and use committee
3
Measurement and observation
3.1
Is it clear what was measured, how it was measured and what the outcomes were?
Pigs were sedated with intramuscular ketamine then intubated and mechanically ventilated with isoflurane anesthesia. Next, a fiberoptic intracranial parenchymal pressure monitor was placed with subsequent continuous monitoring of ICP, electrocardiography, arterial pressure, end-tidal carbon dioxide, and temperature.
3.2
Was the assessment of outcomes blinded?
No
3.3
Was follow up sufficiently long and complete?
Yes, all pigs were monitored in a similar fashion until all four regimens employed.
3.4
Are the measurements valid?
Yes, the newly developed model is effective. It allows measurement of ICP and hemodynamic values throughout RSI modeled on the emergency setting.
3.5
Are the measurements reliable?
Yes
3.6
Are the measurements reproducible?
Yes
4
Presentation of results
4.1
Are the basic data adequately described?
Yes (Table 3, Figures 2 and 3)
4.2
Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
Yes, however the 95% CI on Table 3 are quite wide (imprecise) reflecting the small number of animals studied.
4.3
How large are the effects within a specified time?
All three regimens using succinylcholine demonstrated three-fold higher increases in mean peak changed in ICP during RSI (increasing from 3.6 mm Hg to 12-16 mm Hg). MAP increased concurrently with ICP. All regimens demonstrated increased ICP during intubation peaking at one minute after the start of laryngoscopy and intubation.
4.4
Are the results internally consistent, i.e. do the numbers add up properly?
Yes
5
Analysis
5.1
Are the data suitable for analysis?
Yes
5.2
Are the methods appropriate to the data?
Yes
5.3
Are any statistics correctly performed and interpreted?
Yes, descriptive statistical analysis was performed, with determination of 95% confidence intervals for the primary outcome measure, mean peak change in ICP from baseline.
6
Discussion
6.1
Are the results discussed in relation to existing knowledge on the subject and study objectives?
Yes
6.2
Is the discussion biased?
No
7
Interpretation
7.1
Are the author's conclusions justified by the data?
Yes, a novel animal model offering the potential to further test these long-standing, highly contentious, prophylactic interventions during RSI in larger numbers to better understand potential efficacy and mechanisms of action.
7.2
What level of evidence has this paper presented? (using CEBM levels)
2b
7.3
Does this paper help me to answer my problem?
The current results, although limited by small numbers, seem to suggest no benefit of pre-treatment medications on ICP anytime that succinylcholine is utilized.
8
Implementation
8.1
Can any necessary change be implemented in practice?
No, small sample sizes preclude making definitive conclusions about the various RSI regimens, but the current data should permit future study with more precise power calculations. Future research should also include other commonly utilized RSI agents (Etomidate, Versed, etc.).
8.2
What aids to implementation exist?
The swine model offers a novel opportunity to assess the long-held belief that pre-treatment agents like lidocaine and a defasiculating dose of a non-depolarizing paralytic can alleviate the ICP elevation noted during emergent laryngoscopic intubation.
8.3
What barriers to implementation exist?
ICP is a surrogate marker. The real outcome of importance to patients and clinicians is the neurological recovery. Additional surrogate markers for future study include cerebral oxygenation and metabolism, but ultimately researchers will need to assess the long term neurological recovery and functional independence of these animals (and ultimately patients).
8.4
Are the study patients similar to your own?
No since this was an animal model. In addition, the authors did not induce head injuries (the population on which lidocaine is typically advocated) or use induction agents we usually use. The swine model makes sense, though, because no IRB would approve a similar study in humans and no alternative animal model currently exists.
8.5
Does the paper give any conclusions that will affect what you will offer or tell your patient?
No