Opioid-induced Nausea and Vomiting

SOURCE: Raffa RB, Colucci R, Pergolizzi JV. The effects of food on opioid-induced nausea and vomiting and pharmacological parameters: a systematic review. Postgrad Med 2017;129:698-708.

Opioids are highly effective when administered for appropriate indications. Unfortunately, opioid-induced nausea and/or vomiting (OINV) can limit opioid effectiveness. In the immediate postoperative period, OINV can stress wound integrity and prolong hospital stay. In the outpatient setting, some patients are faced with the dilemma of accepting lesser levels of pain control in exchange for less OINV as they consider whether they should decrease their opioid dosing schedule.

A commonly recommended suggestion to reduce OINV is to take the medication with food. Unfortunately, this recommendation rests on historical dogma rather than well-established data. Raffa et al examined studies about OINV to discern whether administration of opioids with food is effective.

The amount and quality of the literature available was quite limited. While some studies reported complete pharmacokinetics and pharmacodynamics of opioids with and without food, the relationship between opioid plasma levels and symptoms often is omitted.

Although no consistent relationship between OINV and the fed/fasting state was ascertained definitively, the data reviewed suggested that, if anything, high-calorie, high-fat meals tend to exacerbate OINV. Since much of the trial data found that feeding elevates the maximum plasma opioid dose in some patients, and OINV appears to be related to opioid blood levels, it would make sense that feeding might worsen OINV in susceptible individuals.

Currently, methods to address OINV include antiemetics, reduced opioid dose, and switching between opioids to identify agents with less potential to induce OINV. Taking opioids with food was not demonstrated to reduce OINV.


Is It Safe to Use PPIs Long Term?

SOURCE: From the Medical Letter on Drugs and Therapeutics. Safety of long-term PPI use. JAMA 2017;318:1177-1178.

Proton pump inhibitors (PPIs) are among the most widely used medications in the United States, thanks to a generally favorable combination of efficacy, tolerability, and safety. Because such a large portion of the adult population uses PPIs, even if a small fraction experiences an adverse effect, it becomes a potentially important issue.

Probably the most concerning adverse effect of PPIs is increased fracture risk. Although not all individual studies confirmed increased fracture risk from PPIs, a meta-analysis of 18 trials indicated a 26-33% increased risk. Since PPIs are not associated with osteoporosis, the mechanism by which PPIs incur increased fracture risk is unknown.

The FDA sent a warning letter to clinicians about another potentially serious adverse effect of PPIs: hypomagnesemia. To date, only long-term use has been associated with hypomagnesemia, and the mechanism is unknown.

The severity of consequences ranges from simple fatigue to serious events like seizures and arrhythmias. Monitoring magnesium levels may be appropriate, especially in patients also receiving magnesium-depleting medications (e.g., diuretics).

Other rare but important adverse effects reported include acute kidney injury, chronic kidney disease, reduced vitamin B12 levels, iron deficiency, community-acquired pneumonia, and Clostridium difficile infection. The risk:benefit relationship of PPIs is favorable for most patients, but clinicians should remain vigilant for adversities noted above.


The Long-term Picture After Bariatric Surgery

SOURCE: Adams TD, Davidson LE, Litwin SE, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med 2017;377:1143-1155.

While often viewed as a last-resort treatment of obesity, bariatric surgery actually is the only intervention demonstrated to improve obesity-related mortality. Strict criteria for payment by insurers and costs that are inaccessible to most of the uninsured have restricted the population who could benefit from bariatric surgery.

Adams et al enhanced the somewhat sparse literature on long-term outcomes with bariatric surgery. Their 12-year prospective follow-up of patients with severe obesity included a bypass surgery group (n = 418), a group intended for surgery (n = 417) but who ultimately did not undergo surgery (e.g., for lack of insurance coverage), and a matched group of severely obese patients not seeking surgical treatment.

Favorable impact was sustained over the 12-year observation period. Overall weight loss at 12 years was 35 kg (bariatric surgery) vs. 2.9 kg (intended surgery) and 0 kg (no surgery).

For diabetics at the time of bariatric surgery, diabetes remained in remission for more than half of patients at 12 years. The likelihood of new-onset diabetes over 12 years of follow-up among those not diabetic at baseline was reduced by > 90%. The benefits of bariatric surgery are substantial, prompt, and enduring.