In this study, we evaluated the rate of CCU mortality, hospital mortality, 28-days mortality, and the longer of mechanical ventilation duration, CCU stay in AMI patients with sedatives therapy. Among 427 patients, the overall 28-days mortality rate was 23.9%, and mechanical ventilation using was 93.4%. Our study revealed that midazolam using for sedative therapy in AMI patients was significantly associated with longer mechanical ventilation duration and CCU stay, higher rate of CCU mortality, hospital mortality and 28-days mortality when compared to propofol or dexmedetomidine using. There was robust of result in the PSM analysis after adjustment for age, male, hypertension, Scr, MI, beta-blocker, stain, vasopressor, and revascularization. Our finding point to a negative role for midazolam in sedative therapy for AMI critical patients, which has not been reported in past study.
The primary concerns of AMI critical patients are hemodynamic and respiratory suppports. The majority of patients in our study received therapy of mechanical ventilation (93.4%) and vasopressor (78.5%). We speculated that the relatively lower rate of using aspirin (75.6%), clopidogrel (33.3%), and receiving revascularization (77%) were due to practicallly all patients undergoing mechanical ventilation and vasopressor therapy, poor physical condition, and huge risk of bleeding. Sedative therapy is necessary to increase tolerance, reduce discomfort, prevent accidental removal of instrumentation in AMI patients. In this study there were 143 patients in the midazolam using, 272 patients in propofol using, 28 patients in the dexmedetomidine using, and some of them using two or three seditives. Although propofol was reported to have vasorelaxant effect to influence myocardial perfusion and coronary flow reserve , due to impaired left ventricular function in AMI patients, propofol maybe result in aggressive blood pressure reduce in AMI patients. However, in our study, both propofol and dexmedetomidine using in AMI patients for sedative therapy did not show significant associated with 28-days mortality in this study. The sample size of dexmedetomidine using was relatively small in our study, and need more deeply study in future. A randomised placebo-controlled trial in past paper have showed that dexmedetomidine did not decrease postoperative atrial fibrillation in patients recovering from cardiac surgery .
Midazolam was showed closely associated with increased rate of 28-days mortality, and had obviously higher rate of 28-days mortality than propofol or dexmedetomidine using. This phenomenon could be attributed to the following explains. Midazolam has serious cardiorespiratory events and possible paradoxical reactions. Some cardiovascular side effects are premature ventricular contractions, vasovagal episodes, bradycardia, tachycardia, nodal rhythm, as well as variations in blood pressure and pulse rate . Furthermore, midazolam have been reported as inducing coronary artery spasm .
We also found that when compared with propofol or dexmedetomidine, midazolam using presented with increased length of mechanical ventilation and CCU and hospital stay. Long stay in the CCU adds to the burden of health care costs. A meta-analysis demonstrated that dexmedetomidine could reduced the length of ICU stay . Dexmedetomidine was founded to be similar to midazolam in terms of long-term sedation . As aspect of deep sedation, midazolam significantly increased the time at target sedation . It was limitation of our study that a few records of RASS scores were presented, which might attribute to the arousable and light sedation.
PSM is a powerful method to distinguish unbalanced groups. In this study, we chose age, male, hypertension, Scr, MI, beta-blocker, stain, vasopressor, and revascularization as confounding factors. And we found that compared with propofol or dexmedetomidine, midazolam using in AMI patients was still significant associated with increased rate of CCU mortality, hospital mortality, 28-days mortality, and the length of mechanical ventilation, CCU stay.
Several limitations should be reported in this study. First, potential bias remain exist as other unrecorded factors (such as the sedative and ventilation weaning protocol, pre-treatment drugs and door-to-balloon time, the incomplete records of RASS scores and serum tropoin) were not available in MIMIC III database. Instead, we performed the E-value analysis to quantify the potential implications of unmeasured confounders and found that an unmeasured confounder will not change the direction of our result. Secondly, due to the cohort design, only the association instead of causal relationship can be inferred from this study. Third, the sample size of dexmedetomidine using was relatively small, further studies are needed to explore the association between dexmedetomidine and propofol, midazolam and dexmedetomidine.