Prokinetic therapy with erythromycin has no significant impact on blood pressure and heart rate in critically ill patients

Slow gastric emptying and intolerance to nasogastric feeds occurs in up to 40–50% of critically ill patients [1, 2]. Not only does this result in inadequate nutritional support, but it is also a major risk factor for gastro-oesophageal reflux and aspiration, with potential adverse affects on both morbidity and mortality [2, 3]. The currently available therapeutic options for managing delayed gastric emptying and feed intolerance in critically ill patients are: total parenteral nutrient therapy, prokinetic therapy and postpyloric feeding [4, 5]. Of these, treatment with prokinetic agents is efficacious and frequently used as the first-line therapy to avoid the septic complications associated with total parenteral nutrient therapy and the technical demand of postpyloric feeding [4, 5]. Low-dose erythromycin (1–3 mg kg−1), a motilin agonist, is a widely used prokinetic agent in critically ill patients. However, erythromycin has recently been reported to effect human haemodynamics adversely, with a fall in systolic blood pressure (SBP) of 10 ± 9 mmHg 1.5–2.5 h after an oral dose of 300 mg [6]. The mechanism responsible for the hypotension following erythromycin remains unclear. In animals, infusion of motilin was found to induce endothelial-dependent vasodilation and a transient reduction in blood pressure (BP) [7]. As erythromycin leads to an increase in plasma motilin concentrations in humans, it is conceivable that the hypotension associated the drug is related to the endothelium-mediated vasodilation exerted by motilin [8]. Although erythromycin is frequently used in critically ill patients, its haemodynamic effects in this group are unknown. A reduction of 10 mmHg in SBP after erythromycin may not be important in healthy subjects but may be clinically relevant in patients with potential cardiovascular compromise such as the critically ill [6]. This study therefore aimed to examine the acute effects of a single intravenous prokinetic dose of erythromycin on BP) and heart rate (HR) in critically ill patients, who were intolerant to nasogastric feeds and were not on inotropic supportive therapy. Nineteen mechanically ventilated, critically ill patients (age 52 ± 18 years, M:F 10 : 9, Acute Physiology and Chronic Health Evaluation II score 21 ± 6, length of Intensive Care Unit stay 10 ± 9 days) were randomized to either erythromycin (i.v. 200 mg) or placebo (i.v. normal saline) in a cross-over study, 12 h apart. Intolerance to intragastric feeding was defined as vomiting or regurgitation during feeding, or a 6-hourly gastric aspirate > 250 ml [9]. The cut-off gastric aspirate > 250 ml used in this study is a previously published clinical marker of feed intolerance [9, 10]. The majority of patients were sedated with morphine and midazolam and only two patients received propofol alone. Five patients received nasogastric antihypertensive medications (ACE inhibitors n = 3, β-blockers n = 1 and calcium channel blockers n = 1). Continuous lying BP (systolic, diastolic and mean) and HR were measured via an arterial line at 15-min intervals for 60 min before and 180 min after the administration of prokinetic therapy by using an automatic device (TRAM-RAC 4A; General Electric, Milwaukee, WI, USA). A reduction in SBP of >10% from baseline was defined as a clinically significant change. The study was approved by the Local Research Ethics Committee. Each subject gave written informed consent prior to the study. The effects of erythromycin on BP and HR were analysed using a linear mixed effects model fitted to the data. In this model, group status (erythromycin or placebo) and time were treated as fixed effects, while subject was treated as a random effect. Data are expressed as mean ± SD, except in Figure 1, where the error bars represent 95% confidence intervals. A P-value