Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance

N. Q. Nguyen, N. G. Grgurinovich, L. K. Bryant, M. J. Chapman, R. H. Holloway, A. A. Mangoni, R. J. Fraser

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Abstract

Objective: Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients.

Design: Observational comparative study.

Setting: Tertiary critical care unit.

Patients: Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients.

Interventions: Patients received intravenous erythromycin 200 mg twice daily for feed intolerance.

Measurements: Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤250 mL with a feeding rate ≥40 mL/h, was recorded over 7 days.

Results: At day 7, 38% (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = −.47, p = .049) and 7-hr (r = −.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72% sensitivity and 72% specificity, and a 7-hr concentration of ≥0.5 mg/L had 83% sensitivity and 72% specificity in predicting loss of response to erythromycin.

Conclusions: In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.

Original languageEnglish
Pages (from-to)868-871
Number of pages4
JournalCritical Care Medicine
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 2011

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Erythromycin
Critical Illness
Residual Volume
Stomach
Pharmaceutical Preparations
Tachyphylaxis
Sensitivity and Specificity
APACHE
Enteral Nutrition
Tertiary Healthcare
Critical Care
Treatment Failure
Observational Studies
Creatinine
Glucose

Cite this

Nguyen, N. Q., Grgurinovich, N. G., Bryant, L. K., Chapman, M. J., Holloway, R. H., Mangoni, A. A., & Fraser, R. J. (2011). Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance. Critical Care Medicine, 39(4), 868-871. https://doi.org/10.1097/CCM.0b013e318206d57b

Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance. / Nguyen, N. Q.; Grgurinovich, N. G.; Bryant, L. K.; Chapman, M. J.; Holloway, R. H.; Mangoni, A. A.; Fraser, R. J.

In: Critical Care Medicine, Vol. 39, No. 4, 04.2011, p. 868-871.

Research output: Contribution to journalArticle

Nguyen, NQ, Grgurinovich, NG, Bryant, LK, Chapman, MJ, Holloway, RH, Mangoni, AA & Fraser, RJ 2011, 'Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance', Critical Care Medicine, vol. 39, no. 4, pp. 868-871. https://doi.org/10.1097/CCM.0b013e318206d57b
Nguyen, N. Q. ; Grgurinovich, N. G. ; Bryant, L. K. ; Chapman, M. J. ; Holloway, R. H. ; Mangoni, A. A. ; Fraser, R. J. / Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance. In: Critical Care Medicine. 2011 ; Vol. 39, No. 4. pp. 868-871.
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abstract = "Objective: Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients.Design: Observational comparative study.Setting: Tertiary critical care unit.Patients: Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients.Interventions: Patients received intravenous erythromycin 200 mg twice daily for feed intolerance.Measurements: Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤250 mL with a feeding rate ≥40 mL/h, was recorded over 7 days.Results: At day 7, 38{\%} (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = −.47, p = .049) and 7-hr (r = −.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72{\%} sensitivity and 72{\%} specificity, and a 7-hr concentration of ≥0.5 mg/L had 83{\%} sensitivity and 72{\%} specificity in predicting loss of response to erythromycin.Conclusions: In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.",
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T1 - Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance

AU - Nguyen, N. Q.

AU - Grgurinovich, N. G.

AU - Bryant, L. K.

AU - Chapman, M. J.

AU - Holloway, R. H.

AU - Mangoni, A. A.

AU - Fraser, R. J.

PY - 2011/4

Y1 - 2011/4

N2 - Objective: Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients.Design: Observational comparative study.Setting: Tertiary critical care unit.Patients: Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients.Interventions: Patients received intravenous erythromycin 200 mg twice daily for feed intolerance.Measurements: Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤250 mL with a feeding rate ≥40 mL/h, was recorded over 7 days.Results: At day 7, 38% (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = −.47, p = .049) and 7-hr (r = −.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72% sensitivity and 72% specificity, and a 7-hr concentration of ≥0.5 mg/L had 83% sensitivity and 72% specificity in predicting loss of response to erythromycin.Conclusions: In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.

AB - Objective: Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients.Design: Observational comparative study.Setting: Tertiary critical care unit.Patients: Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients.Interventions: Patients received intravenous erythromycin 200 mg twice daily for feed intolerance.Measurements: Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤250 mL with a feeding rate ≥40 mL/h, was recorded over 7 days.Results: At day 7, 38% (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = −.47, p = .049) and 7-hr (r = −.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72% sensitivity and 72% specificity, and a 7-hr concentration of ≥0.5 mg/L had 83% sensitivity and 72% specificity in predicting loss of response to erythromycin.Conclusions: In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.

U2 - 10.1097/CCM.0b013e318206d57b

DO - 10.1097/CCM.0b013e318206d57b

M3 - Article

VL - 39

SP - 868

EP - 871

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

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