Fifty-five of 118 patients (46%) survived to hospital discharge and 21 of 118 (18%) had favorable neurologic outcome. Adjusting for shockable initial rhythm, OHCA, and PCAC score (P < 0.05 in forward stepwise regression), we found that CVI-6h was associated with survival to hospital discharge (OR 0.68; 95% CI 0.53, 0.87; P = 0.002) (Fig. 2A). No exposure variable assessed was associated with neurologic outcome (Fig. 2B). Both models had acceptable fit.
All four groups displayed similar distributions of baseline MAP and 6-h average MAP (Fig. 3A). There were 38 patients in the low fluid/vasopressor group, 21 in the low fluid/high vasopressor group, 19 in the high fluid/low vasopressor group, and 40 in the high fluid/vasopressor group. Only one patient received any dobutamine in the first 6 h and none received milrinone. There was a trend toward higher baseline heart rate and CVI in the high fluid/vasopressor group and higher MAP in the low fluid/vasopressor group (Table 1). Compared with the low vasopressor group (6 h mean CVI ± SD = 0.08 ± 0.23), the high vasopressor group received on average significantly greater exposure to pressors (6 h mean CVI ± SD = 4.23 ± 3.27; P < 0.001) during the initial 6 h of resuscitation. Likewise, compared with the low fluid intake group, (6 h mean intake ± SD = 270.3 ± 222.1 mL), the high fluid intake group received on average significantly greater volume (6 h mean intake ± SD = 1195.1 ± 1163.5 mL; P < 0.001).
Our data address some limitations of previous work by examining how MAP was attained (fluid intake vs. vasopressors). Our findings suggest that high vasopressor use to achieve higher MAP may be detrimental. Figure 2B demonstrates the independent association between increased CVI and worsened survival, whereas Figure 3 highlights the same association irrespective of the amount of fluids given. Several recent studies have also identified associations between vasopressors and poor outcomes (7,28). It may be that pharmacologic vasoconstriction, intended to improve vital organ perfusion, reduces microvascular perfusion of those same vital tissues. The exact mechanism for the adverse effect of vasopressors is unknown. Increased vasopressor requirements may reflect poor peripheral vascular responsiveness or just severe underlying shock.
It is physiologically plausible that increasing intravascular volume using fluids could increase cardiac output and tissue perfusion without constricting arteriolar beds and avoiding shunting (as occurs with vasopressors) (30). Our findings suggest the early use of fluids preferentially over vasopressors, assuming volume responsiveness, could improve outcomes in cardiac arrest patients in the ICU. The initial liberal use of fluids (30 mL/kg) and subsequent titration (based on fluid responsiveness) is already advocated by international committees for resuscitation from septic shock (31). Although prehospital use of aggressive fluid resuscitation may have adverse effects after ROSC (32), our definition of “early” was the ICU course which began often an hour after ROSC. As one gets further from ROSC and the effects of drugs given for resuscitation and mechanical compressions are more distant, the heart may better tolerate an increase in preload without precipitating heart failure. Our findings at least provide equipoise when considering liberal fluid resuscitation in the early post-ROSC hours despite probable postarrest myocardial dysfunction (2–4).
Our results do not support the indiscriminate use of IV fluids as the primary means of sustaining a target MAP. Aggressive fluid resuscitation carries risks, including both pulmonary edema and even re-arrest (33). Furthermore, use of liberal fluid resuscitation in patients unlikely to be fluid responsive can worsen outcomes (34). Cardiac arrest patients with a significant component of systemic inflammation-mediated distributive shock (5) would likely have vasoplegia and require some degree of vasopressors to maintain vascular tone independent of the impact of fluids on cardiac output. Exactly what that balance should be has not been defined, but may be guided by frequent assessment of fluid responsiveness. Practically speaking, ICU nurses are often allowed to titrate vasopressors to a target MAP, but are not given similar liberty to administer fluids. Thus, increasing vasopressor dosage to maintain MAP may get priority over fluid boluses for practical rather than physiologic reasons. Our data suggest that the singular use of vasopressors to target MAP levels post-cardiac arrest may be less beneficial than a matched fluid-and-vasopressor approach, which should prompt clinicians to design protocols aimed at optimizing the complex hemodynamics of post-cardiac arrest syndrome (9).
Our retrospective study design and the size of our dataset both limit the conclusions we can draw. The decision to target higher MAP and whether to use fluids or vasopressors was at the discretion of individual physicians and nurses, so we cannot know all of the variables that influenced treatment decisions. A formal, prospective assessment comparing resuscitation strategies is needed to define optimal MAP, fluid and vasopressor targets, and the utility of a tailored approach to account for the clinical heterogeneity encountered in postarrest patients. Our work does provide some suggestion of what constitutes an “optimal” MAP, and the consistency of the findings through differing analytic approaches provides some strength. The use of a summary scoring system such as CVI as a measure of vasopressor dependence is a limitation since it does not reflect subtle differences among patients with similar CVI. Our use of lactate clearance as a measure of shock resolution was somewhat limited by the smaller number of patients in whom serial lactate levels were measured, and it is unclear how well our calculation of lactate clearance approximates shock resolution. It should be noted that in our own dataset, lactate clearance did not associate with better outcome (data not shown) although it has in other groups’ prior work (15–17,24,25). CPC was utilized in this study as a measure of neurologic outcome due to its universal availability among these patients. However, CPC does not correlate well with other measures of neurologic outcome such as discharge location or modified Rankin Scale. Neurologic outcome improves over time with ongoing rehabilitation or therapy (35). This work addresses an important gap in the present literature by evaluating the impact of MAP, vasopressor use, and fluid use on shock resolution and clinical outcomes.
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