Enteral nutrition in septic shock: a call for a paradigm shift.
Current opinion in critical care
PURPOSE OF REVIEW:The purpose of this review is to identify contemporary evidence evaluating enteral nutrition in patients with septic shock, outline risk factors for enteral feeding intolerance (EFI), describe the conundrum of initiating enteral nutrition in patients with septic shock, appraise current EFI definitions, and identify bedside monitors for guiding enteral nutrition therapy. RECENT FINDINGS:The NUTRIREA-2 and NUTRIREA-3 trial results have better informed the dose of enteral nutrition in critically ill patients with circulatory shock. In both trials, patients with predominant septic shock randomized to receive early standard-dose nutrition had more gastrointestinal complications. Compared to other contemporary RCTs that included patients with circulatory shock, patients in the NUTRIREA-2 and NUTRIREA-3 trials had higher bowel ischemia rates, were sicker, and received full-dose enteral nutrition while receiving high baseline dose of vasopressor. These findings suggest severity of illness, vasopressor dose, and enteral nutrition dose impact outcomes. SUMMARY:The provision of early enteral nutrition preserves gut barrier functions; however, these benefits are counterbalanced by potential complications of introducing luminal nutrients into a hypo-perfused gut, including bowel ischemia. Findings from the NUTRIREA2 and NUTRIREA-3 trials substantiate a 'less is more' enteral nutrition dose strategy during the early acute phase of critical illness. In the absence of bedside tools to guide the initiation and advancement of enteral nutrition in patients with septic shock, the benefit of introducing enteral nutrition on preserving gut barrier function must be weighed against the risk of harm by considering dose of vasopressor, dose of enteral nutrition, and severity of illness.
10.1097/MCC.0000000000001134
Vasopressors and Nutrition Therapy: Safe Dose for the Outset of Enteral Nutrition?
Critical care research and practice
BACKGROUND AND AIMS:Patients with hemodynamic instability need to receive intensive treatment as fluid replacement and vasoactive drugs. In the meantime, it is supposed to initiate nutritional therapy within 24 to 48 hours after admission to the intensive care unit (ICU), as an essential part of patient's intensive care and better outcomes. However, there are many controversies tangential to the prescription of enteral nutrition (EN) concomitant to the use of vasopressor and its doses. In this way, the present study aimed to identify what the literature presents of evidence to guide the clinical practice concerning the safe dose of vasopressors for the initiation of nutritional therapy in critically ill patients. METHODS:This review was carried out in PubMed, ProQuest, Web of Science, and Medline databases. The descriptors were used to perform the search strategy: Critical Care, Intensive Care Units, Vasoconstrictor Agents, and Enteral Nutrition. Inclusion criteria were patients of both genders, over 18 years of age, using vasoactive drugs, with the possibility of receiving EN therapy, and articles written in English, Portuguese, and Spanish. In addition, exclusion criteria were case reports, non-papers, and repeated papers. RESULTS:10 articles met our inclusion criteria. CONCLUSION:It was observed that there are many controversies about the supply of EN in critically ill patients using vasopressor, especially about the safe dose, and it was not possible to identify a cutoff value for the beginning therapy. Despite the drug doses, clinical signs are still the most important parameters in the evaluation of EN tolerance.
10.1155/2020/1095693
Overcoming challenges to enteral nutrition delivery in critical care.
Current opinion in critical care
PURPOSE OF REVIEW:Existing data and all ICU nutrition guidelines emphasize enteral nutrition (EN) represents a primary therapy leading to both nutritional and non-nutritional benefits. Unfortunately, iatrogenic malnutrition and underfeeding is virtually ubiquitous in ICUs worldwide for prolonged periods post-ICU admission. Overcoming essential challenges to EN delivery requires addressing a range of real, and frequently propagated myths regarding EN delivery. RECENT FINDINGS:Key recent data addresses perceived challenges to EN including: Adequately resuscitated patients on vasopressors can and likely should receive trophic early EN and this was recently associated with reduced mortality; Patients paralyzed with neuromuscular blocking agents can and should receive early EN as this was recently associated with reduced mortality/hospital length of stay; Proned patients can safely receive EN; All ICU nutrition delivery, including EN, should be objectively guided by indirect calorimetry (IC) measures. This is now possible with the new availability of a next-generation IC device. SUMMARY:It is the essential implementation of this new evidence occurs to overcome real and perceived EN challenges. This data should lead to increased standardization/protocolization of ICU nutrition therapy to ensure personalized nutrition care delivering the right nutrition dose, in the right patient, at the right time to optimize clinical outcome.
10.1097/MCC.0000000000000801
Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis.
Krejci Vladimir,Hiltebrand Luzius B,Sigurdsson Gisli H
Critical care medicine
OBJECTIVE:The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN:Random order, cross-over design. SETTING:University laboratory. SUBJECTS:Eight sedated and mechanically ventilated pigs. INTERVENTIONS:Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS:During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS:Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.
10.1097/01.CCM.0000215834.48023.57
Comparison of dopamine and norepinephrine in the treatment of shock.
De Backer Daniel,Biston Patrick,Devriendt Jacques,Madl Christian,Chochrad Didier,Aldecoa Cesar,Brasseur Alexandre,Defrance Pierre,Gottignies Philippe,Vincent Jean-Louis,
The New England journal of medicine
BACKGROUND:Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS:In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS:The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS:Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)
10.1056/NEJMoa0907118
Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.
Critical care medicine
OBJECTIVES:To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN:Review and task force position statements with necessary guidance. SETTING:A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS:A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS:The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS:There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS:A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.
10.1097/CCM.0000000000006176
Vasoactive substances and their effects on nutrition in the critically ill patient.
Allen John M
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
Critically ill patients often require specialized nutrition via the enteral route. The benefits of enteral feeding, particularly early in the care of the critically ill patient, are well documented. Controversy exists regarding the provision of enteral nutrition (EN) in critically ill patients with hemodynamic instability who require vasopressors or inotropes. Concerns center on the potential for gut ischemia that may develop in the face of an imbalance between oxygen supply and demand. Current guidelines offer some guidance as to when to it is safe to initiate enteral feeding in patients on vasopressors, but the decision on when to start EN in hemodynamically unstable patients requiring vasoactive substances remains a clinical dilemma for most critical care practitioners. This review focuses on the effects of vasoactive substances such as pressors and inotropes on the gastrointestinal tract, as well as their use in combination with EN.
10.1177/0884533612443989
Early enteral nutrition in critically ill patients with hemodynamic instability: an evidence-based review and practical advice.
Yang Shuofei,Wu Xingjiang,Yu Wenkui,Li Jieshou
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
Early enteral nutrition (EEN) in critically ill patients is associated with significant benefit as well as elevated risk of complications. Concomitant use of EEN with vasopressors has been associated with nonocclusive bowel necrosis in critically ill patients with hemodynamic instability. The decision when to initiate enteral nutrition in hemodynamically unstable patients that require vasoactive substances remains a clinical dilemma. This review summarizes the effect of EEN and vasoactive agents on gastrointestinal blood flow and perfusion in critically ill patients, based on current evidence. Animal and clinical data involving simultaneous administration of EEN and vasoactive agents for hemodynamic instability are reviewed, and the factors related to the safety and effectiveness of EEN support in this patient population are analyzed. Moreover, practical recommendations are provided. Additional randomized clinical trials are warranted to provide cutting-edge evidence-based guidance about this issue for practitioners of critical care.
10.1177/0884533613516167
Vasopressors in septic shock: which, when, and how much?
Shi Rui,Hamzaoui Olfa,De Vita Nello,Monnet Xavier,Teboul Jean-Louis
Annals of translational medicine
In addition to fluid resuscitation, the vasopressor therapy is a fundamental treatment of septic shock-induced hypotension as it aims at correcting the vascular tone depression and then at improving organ perfusion pressure. Experts' recommendations currently position norepinephrine (NE) as the first-line vasopressor in septic shock. Vasopressin and its analogues are only second-line vasopressors as strong recent evidence suggests no benefit of their early administration in spite of promising preliminary data. Early administration of NE may allow achieving the initial mean arterial pressure (MAP) target faster and reducing the risk of fluid overload. The diastolic arterial pressure (DAP) as a marker of vascular tone, helps identifying the patients who need NE urgently. Available data suggest a MAP of 65 mmHg as the initial target but a more individualized approach is often required depending on several factors such as history of chronic hypertension or value of central venous pressure (CVP). In cases of refractory hypotension, increasing NE up to doses ≥1 µg/kg/min could be an option. However, current experts' guidelines suggest to combine NE with other vasopressors such as vasopressin, with the intent to rising the MAP to target or to decrease the NE dosage.
10.21037/atm.2020.04.24
Tolerability of Enteral Nutrition in Mechanically Ventilated Patients With Septic Shock Who Require Vasopressors.
Merchan Cristian,Altshuler Diana,Aberle Caitlin,Papadopoulos John,Schwartz David
Journal of intensive care medicine
PURPOSE:Enteral nutrition (EN) is often held in patients receiving vasopressor support for septic shock. The rationale for this practice is to avoid mesenteric ischemia. The objective of this study is to evaluate the tolerability of EN in patients with septic shock who require vasopressor support and determine factors associated with tolerance of EN. MATERIALS AND METHODS:This was a single-center retrospective review of adult patients admitted to the intensive care unit with a diagnosis of septic shock and an order for EN. The primary outcome was EN tolerance. Secondary outcomes included time to initiation of EN from the start of vasopressor(s), length of stay, and mortality. RESULTS:A total of 120 patients were included. Sixty-two percent of patients tolerated EN. The most common reason for intolerance of EN was gastric residuals > 250 mL (74%). No reports of mesenteric ischemia were observed. A multivariate analysis demonstrated that patients with septic shock initiating EN within 48 hours and receiving norepinephrine-equivalent doses of 0.14 μg/kg/min or less were more likely to tolerate EN. CONCLUSION:Based on our observation, early EN may be tolerated and safely administered in patients with septic shock who are adequately fluid resuscitated and receive doses of < 0.14 μg/kg/min of norepinephrine equivalents.
10.1177/0885066616656799
Catecholamine use is associated with enterocyte damage in critically ill patients.
Piton Gaël,Cypriani Benoit,Regnard Jacques,Patry Cyrille,Puyraveau Marc,Capellier Gilles
Shock (Augusta, Ga.)
Small bowel damage is frequent but underdiagnosed among critically ill patients with shock. High catecholamine doses may have a deleterious effect on mesenteric blood flow. Plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker of enterocyte damage, whereas plasma citrulline concentration is a marker of functional enterocyte mass. We hypothesized that high doses of catecholamines in critically ill patients may be associated with enterocyte damage. This study aimed to determine the link between catecholamine use and dose with enterocyte damage. This is a prospective observational study performed in a large regional university teaching hospital. Critically ill patients requiring epinephrine and/or norepinephrine at admission to a medical intensive care unit (ICU) were included, as well as controls not receiving catecholamines. We evaluated at admission plasma I-FABP and citrulline concentrations, abdominal perfusion pressure (APP), and variables relating to prognosis and treatment. Patients were categorized according to the quartiles of catecholamine dose at ICU admission. Sixty critically ill patients receiving catecholamines and 27 not receiving catecholamines were included. Plasma I-FABP was higher among patients receiving catecholamine than in controls. Among patients receiving catecholamines, a dose of 0.48 γ kg min or more at ICU admission was associated with a higher I-FABP concentration. A Sepsis-related Organ Failure Assessment score higher than 11 and plasma I-FABP more than 524 pg mL at ICU admission were independently associated with 28-day mortality (odds ratio, 4.0 [1.24-12.95] and odds ratio, 4.90 [1.44-16.6], respectively). Catecholamine use is associated with I-FABP elevation in critically ill patients. Critically ill patients receiving more than 0.48 γ kg min of epinephrine and/or norepinephrine at ICU admission have high I-FABP concentrations. This suggests that enterocyte damage reflects the severity of shock, and an adverse effect of catecholamines per se is possible.
10.1097/SHK.0000000000000327
Tolerability and safety of enteral nutrition in critically ill patients receiving intravenous vasopressor therapy.
Mancl Erin E,Muzevich Katie M
JPEN. Journal of parenteral and enteral nutrition
BACKGROUND:Enteral nutrition (EN) is recommended within the first 24-48 hours following admission to an intensive care unit (ICU) once resuscitation and hemodynamic stability have been achieved; however, hemodynamic stability is not well defined. OBJECTIVE:To evaluate the tolerability and safety of EN in critically ill patients receiving intravenous (IV) vasopressor therapy. METHODS:A retrospective medical record review was conducted in an urban academic medical center and included adult ICU patients from 2011 who received concomitant EN and IV vasopressor therapy for ≥1 hour. EN tolerance was defined as an absence of gastric residuals ≥300 mL, emesis, positive finding on abdominal imaging, and evidence of bowel ischemia/perforation. RESULTS:Two hundred fifty-nine patients received 346 episodes of concomitant EN and IV vasopressor therapy. Overall EN tolerability was 74.9%. Adverse events included rising serum lactate (30.6%), elevated gastric residuals (14.5%), emesis (9.0%), positive finding on kidney/ureter/bladder radiograph (4.3%), and bowel ischemia/perforation (0.9%). An inverse relationship was found between maximum norepinephrine equivalent dose and EN tolerability (12.5 mcg/min for patients who tolerated EN vs 19.4 mcg/min, P = .0009). This relationship remained statistically significant after controlling for other variables (P = .019). Patients who tolerated EN were less likely to have received dopamine (63.8% vs 77.6%, P = .018) or vasopressin (58.9% vs 77.9%, P = .0027). These patients received concomitant therapy for less time and received more nutrition. CONCLUSIONS:Most patients receiving IV vasopressor therapy tolerate EN. Tolerability was related to the maximum cumulative vasopressor dose and may be related to the specific vasopressor administered.
10.1177/0148607112470460
Norepinephrine Contributes to Enterocyte Damage in Septic Shock Patients: A Prospective Cohort Study.
Habes Quirine L M,van Ede Lisa,Gerretsen Jelle,Kox Matthijs,Pickkers Peter
Shock (Augusta, Ga.)
OBJECTIVES:In septic patients, both systemic inflammation and splanchnic hypoperfusion may cause enterocyte damage. Catecholamines may exert additional detrimental effects on mesenteric blood flow in these patients, and thereby contribute to this damage. Enterocyte damage itself results in impairment of gut barrier function and consequent translocation of bacteria/toxins. This may contribute to multiple organ failure and death by sustaining or amplifying the systemic inflammatory response. The aim of the study was 2-fold: to investigate which factors contribute to enterocyte damage in septic patients, and to assess whether enterocyte damage is associated with a sustained or amplified systemic inflammatory response. METHODS:In this prospective observational cohort study in 129 patients with septic shock admitted to the ICU, we serially measured plasma levels of Intestinal Fatty Acid-Binding Protein (I-FABP, a marker for enterocyte damage) and of cytokines Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-y, Interleukin (IL)-1β, IL-6, IL-8, IL-1 Receptor Antagonist (RA), and IL-10. Clinical data were collected from electronic patient files. RESULTS:A total of 129 patients were included in the study. The median age of the patients was 67 years [56-74]. The median norepinephrine infusion rate was 0.2 μg/kg/min [0.1-0.5]. Overall, 28-day mortality was 31 (24%). Similar to previous work, I-FABP levels at admission were independently associated with mortality (odds ratio 3.101 [1.138-8.448]). Acute Physiology and Chronic Health Evaluation II score and an increase in norepinephrine infusion rate between days 1 and 3 were independently associated with area under curve I-FABP levels, whereas mean arterial pressure and creatinine levels were not. No correlations were found between any of the measured cytokines and plasma I-FABP levels. Furthermore, high I-FABP levels were not related with the subsequent course of cytokine levels. CONCLUSIONS:In patients with septic shock, norepinephrine use is associated with more enterocyte damage. Although enterocyte damage is associated with increased 28-day mortality, it is not associated with a sustained or amplified systemic inflammatory response.
10.1097/SHK.0000000000000955
Differences in effect of early enteral nutrition on mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: A propensity-matched analysis.
Ohbe Hiroyuki,Jo Taisuke,Matsui Hiroki,Fushimi Kiyohide,Yasunaga Hideo
Clinical nutrition (Edinburgh, Scotland)
BACKGROUND & AIMS:Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. METHODS:Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 μg/kg/min), medium- (0.1-0.3 μg/kg/min), and high-dose (≥0.3 μg/kg/min) noradrenaline groups. RESULTS:We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, -2.9%; 95% confidence interval [CI], -4.5% to -1.3%) and in the medium-dose noradrenaline group (risk difference, -6.8%; 95% CI, -9.6% to -4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, -1.4%; 95% CI, -7.4%-4.7%). CONCLUSIONS:Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in those requiring high-dose noradrenaline.
10.1016/j.clnu.2019.02.020
The patient with circulatory shock: to feed or not to feed?
Cresci Gail,Cúe Jorge
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
Controversy continues to surround the appropriate form and timing of nutrition support for the patient with circulatory shock. Clinical studies have demonstrated improvements in outcome with the administration of enteral nutrition to critically ill patients; however, the provision of enteral nutrition to critically ill patients with ongoing shock remains controversial. This article reviews gut perfusion during normal states and during circulatory shock as well as alterations in perfusion when enteral feeding is provided. Pharmaconutrients studied during ischemia and reperfusion are discussed.
10.1177/0884533608323431