Research: Creating Your Own Experimental Design

I am a graduate of Eastern Mennonite University’s M.A. in Biomedicine program. A part of the curriculum requires that a student design their own research project using the fundamentals of the scientific process. I have included my entire design along with a snapshot for each of the outcomes. This is something I am passionate about and plan to pursue as a future practitioner. Clinical research is extremely relevant and leads to better patient outcomes. Let me know if any of you have questions or please post a comment!

Background:

When patients experience trauma in the field, pre-hospital rapid sequence intubation (RSI) is often the course of action. Despite the fact that RSI is associated with favorable outcomes it also carries the risk of increased hypotension and bradycardia. Ketamine is a very attractive anesthetic for RSI because it does not impair breathing and is thought to increase catecholamine levels, ultimately increasing heart rate and blood pressure. Thus, if a patient demonstrates bradycardia and hypotension as a result of intubation, ketamine may be able to the raise heart rate and blood pressure closer to normal levels. But the research literature regarding the effects of ketamine on patients with varying baseline hemodynamic measurements is variable and somewhat unclear. Some studies showed the use of ketamine raises both HR and BP, while others showed the opposite. As a result, it may be difficult for first responders, ER personnel and trauma surgeons to determine who will benefit from ketamine’s hypertensive and tachycardic effects versus those who will develop hypotension and/or bradycardia. Therefore, we sought to clarify the determinants of the ketamine response in patients undergoing rapid sequence induction of anesthesia. 3 post-ketamine primary outcomes / or responses were examined: 1) development of bradycardia; 2) development of hypotension 3) development of hypertension. The predictors / risk factors for the ketamine response that we tested included: Subject age, category (trauma vs. medical), and pre-ketamine vital signs (HR, SBP, DBP, MAP, and SI). We also studied the effect of ketamine dose on the response.

We hypothesized the following:

Hypothesis 1: Vital signs prior to administration of ketamine (i.e. BP and HR) predict the development of hypotension and/or bradycardia in patients undergoing RSI;

Hypothesis 2: The relationship between baseline vital signs and the development of hypotension, hypertension, and bradycardia is moderated by the dose of ketamine given.

Methods:

Data was obtained from PHI Air medical group (a Helicopter emergency medical service that safely transfers trauma and emergency patients across the nation). A total of 1516 subjects were enrolled, out of which 730 were medical patients and 786 were trauma patients. Study subjects received ketamine doses that were categorized into four dose groups: < 100 mg/ml, 101-150 mg/ml, 151-200 mg/ml, and >200 mg/ml. Data regarding subject demographics, patient category (medical vs. trauma), drug doses and hemodynamic measures were obtained and used in the analysis.

Results:

1) Predictors of bradycardia:

• Older age was a predictor of post-ketamine bradycardia (Patients who developed bradycardia were on average 13 years older than those who didn’t).

• Medical patients were more likely to develop bradycardia than trauma patients.

• Patients who developed bradycardia had lower baseline pre-ketamine vitals signs (SBP, DBP, MAP, HR) and higher Baseline SIs.

• Higher doses of ketamine were also associated with bradycardia.

2) Predictors of hypotension:

• Older age was a predictor of post-ketamine hypotension (those who developed hypotension were on average 10 years older than those who didn’t)

• Patients who developed hypotension were more likely to be medical patients.

• Lower pre-ketamine (baseline) SBP, DBP, MAP, and SI were associated with development of hypotension, while higher HRs at baseline were associated with the development of hypotension.

3) Predictors of hypertension:

• Younger age was associated with development of hypertension. (were on average 4 years younger)

• Trauma patients were more likely to develop hypertension than medical patients.

• Higher baseline SBP, DBP, MAP, and shock indices were associated with the development of post-ketamine hypertension.

Note: Higher doses of ketamine were significantly associated with bradycardia and hypertension.

Conclusion:

We found that older age, lower baseline vitals, and being a medical patient vs. a trauma patient is more likely to predict the development of bradycardia and/ or hypotension following the administration of ketamine during RSI. On the other hand, younger subjects, higher baseline vitals and trauma patients were more likely to develop hypertension following ketamine administration. It also seemed that higher doses of ketamine were associated with developing bradycardia and hypotension / or hypertension. Knowing how baseline subject characteristics including vitals signs effect the response to ketamine administration will help first responders and trauma/ emergency care personnel better identify who may benefit from the administration of ketamine versus those who may potentially develop adverse events such as hypotension and bradycardia. This will enable healthcare professionals to improve upon current mortality and morbidity rates associated with RSI.