Clinical PotpourriDoes high-dose vasopressor therapy in medical intensive care patients indicate what we already suspect?☆
Introduction
As practicing intensivists, we intuitively appreciate when a patient's situation is becoming dire. We spend time at the bedside, examine the patient, order tests, and view the trend in the physiological parameters. In this setting, we may observe the inexorable escalation of vasopressor support in an attempt to maintain organ perfusion [1]. Vasopressor therapy is commonly used to defend organ perfusion when there is an inadequate response to intravascular volume repletion in patients in the intensive care unit (ICU). Indeed vasopressor therapy is recommended for septic shock, in particular [2], [3], and it has also been shown to favorably influence outcome in patients with septic shock [4]. However, guidelines are lacking as to the maximal dose recommended for subgroups of critically ill patients.
Given the high incidence of shock and septic shock, in particular, presenting to ICUs [5], vasopressor therapy is very commonly used. However, at some point and in some patients, it becomes evident that there is poor or no response to vasopressor therapy, such as high-dose adrenaline, noradrenaline, and/or vasopressin. Most intensivists recognize this scenario as one in which the patient is unlikely to do well and indeed may make the decision to withdraw therapy on the grounds of medical futility. The literature is scant in terms of the prognostic predictive value of high-dose vasopressor therapy in this setting [6], [7]. This issue is somewhat obscured by the concept of the self-fulfilling prophesy represented by withdrawal of treatment deemed to be futile (ie, “non-response to high-dose vasopressor therapy is a good indicator that the patient is not able to survive the current illness,” so treatment is withdrawn and the patient dies).
We were interested in what actually happens to patients receiving high-dose vasopressor therapy in the clinical setting where treatment withdrawal is not practiced. The authors work in a cultural setting where withdrawal of treatment is not carried out, regardless of the perceived futility of ongoing intensive care treatment. The outcome of patients, in terms of mortality, is therefore not affected by the practice of withdrawal of therapy and represents a “true” outcome.
We undertook an observational study over the period April 27, 2008, to August 3, 2010, examining the outcome of patients admitted to our ICU who received no vasopressors, lower-dose vasopressors, or high-dose vasopressors.
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Materials and methods
We applied to and received from the institutional ethics committee a waiver of the requirement for informed consent (review of records only and use of non-identified patient data). Data were then obtained from our unit database on all patients admitted over the period April 27, 2008, to August 3, 2010, representing 917 patients. Detailed data were then collected for patients receiving noradrenaline or adrenaline, being the vasopressors most commonly used in our unit. Of the 917 patients
Results
The results shown in Table 1 indicate a significant difference (P < .05) between the low- and high-dose vasopressor groups for age (younger patients received high dose) and APACHE II score (sicker patients in the high-dose group). The high-dose vasopressor group also had more patients with hematologic malignancies, but with less preexisting cancer. High-dose vasopressor therapy was also associated with more vasopressin use, not surprising given that vasopressin is used for refractory
Discussion
We found that the use of high-dose vasopressor therapy in the medical ICU (MICU) is associated with a very high mortality of 84.3% in the ICU and 90% for the hospital admission in our population of adult medical intensive care patients. We regard this as “true outcome” because we do not practice withdrawal of life support drugs and interventions. Our outcome data for patients requiring high-dose vasopressors represent a 4-fold increase in mortality over the general MICU population during the
Conclusion
We have shown that the requirement for high-dose vasopressor therapy is a predictor for poor outcome, and more than 90% of patients in our MICU who received more than 40 μg/min of vasopressors at any time during the ICU admission died. Guidelines are lacking for the acceptable range of high-dose vasopressors and inotropes in specific patient subgroups.
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Cited by (30)
The Relationship Between Norepinephrine Equivalent Dose of Vasopressors Within 24 Hours From the Onset of Septic Shock and In-Hospital Mortality Rate
2023, ChestCitation Excerpt :In the present study, the in-hospital mortality rate dramatically and continuously increased as the maximum NEE dose in the first 24 h of shock onset increased, even after adjustment for the patient baseline characteristics and the severity score. Although the relationships between high-dose vasopressors and death have been described previously in smaller cohorts,4-6 our study is the largest cohort of patients with septic shock who condition required a maximum NEE of ≥ 1.0 μg/kg/min in the first 24 h after shock onset. Our study has two important implications.
Hitting the Vasopressor Ceiling: Finding Norepinephrine Associated Mortality in the Critically Ill
2021, Journal of Surgical ResearchCitation Excerpt :One observational cohort study demonstrated a positive correlation between number of vasopressors required and mortality rate, with an observed mortality rate of 92% in the setting of three vasopressors at maximum infusion.8 Another retrospective study showed that patients who received more than 40 mcg/min of any vasopressor suffered a 90% in-hospital mortality rate.12 In spite of the evidence that high vasopressor doses correlate with mortality, there is currently no guidance regarding what norepinephrine dose correlates with clinical futility.
Methylene Blue for Vasoplegia During Extracorporeal Membrane Oxygenation Support
2021, Journal of Cardiothoracic and Vascular AnesthesiaAngiotensin II in Vasodilatory Shock
2019, Critical Care ClinicsCitation Excerpt :By one estimate, only 17% of patients with septic shock requiring vasopressor therapy of greater than or equal to 1 mcg/kg/min of norepinephrine-equivalent dosing survive to 90 days.12 In addition, high-dose catecholamine therapy has been shown to be independently predictive of mortality after controlling for many factors, including severity of illness.33 Catecholamine monotherapy is also associated with significant cardiac side effects, morbidity, and mortality, an effect that is correlated with the cumulative dose of catecholamines, the number of different catecholamines used, and the duration of therapy.34
Regional differences in the treatment of refractory vasodilatory shock using Angiotensin II in High Output Shock (ATHOS-3) data
2019, Journal of Critical CareCitation Excerpt :As with the case of combination vasopressors, the guidelines remain unclear on timing of steroid initiation, in relation to vasopressor dosing. Part of this issue is the lack of clarity on what constitutes catecholamine-resistant hypotension [2,28,33-35]. The ATHOS-3 trial designated a NED of >0.2 μg/kg/min based on a calculated 50% mortality using SOFA scores, but other higher doses that cited nearly 80–100% mortality have been proposed as well [33,34,36].
Intensity of Vasopressor Therapy for Septic Shock and the Risk of In-Hospital Death
2017, Journal of Pain and Symptom ManagementCitation Excerpt :Given the high mortality associated with septic shock, a method of distinguishing patients who do or do not have a reasonable chance of surviving with aggressive treatment could help clinicians and families weigh the options and make informed decisions. Anecdotal observations at our institution and a few published reports11–13 have suggested that the chance of surviving septic shock decreases as the intensity of vasopressor therapy needed to treat the condition escalates. The present observational cohort study examined in-hospital mortality as a function of therapeutic intensity by analyzing vasopressor use and survival status in a consecutive series of adult patients with septic shock who were admitted to Winthrop University Hospital over a four-year period.
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Conflict of interest: None of the authors have any conflict of interest in the conduct or reporting of the research described in this manuscript.