Effect of nonsteroidal anti-inflammatory medicines on kidney function in patients with normal kidney function undergoing surgery

What is the issue?

Nonsteroidal anti-inflammatory drugs (NSAIDs) offer effective pain relief following surgery. Acute kidney injury (AKI) is the rapid loss of kidney function. It is associated with high death rate. NSAIDs can lead to AKI in up to 5% of patients using them. This is increased when there are other stresses placed on the kidney such as surgery. It is therefore important to establish whether these drugs are safe to use as pain relief in patients undergoing surgery. The aim of the review was to examine whether NSAIDs lead to increased rates of AKI in patients with normal kidney function undergoing surgery. We also aimed to examine whether NSAIDs were associated with higher death rates, increased length of hospital stay and need for dialysis.

What did we do?

We updated a previous review searching the Cochrane Kidney and Transplant Specialised Register until 4 January 2018 for randomised controlled trials (RCTs) comparing NSAIDs with placebo in patients with normal kidney function undergoing surgery.

What did we find?

We identified 26 studies studying 8835 participants. Risk of bias was high in 17, unclear in six studies and low in three studies. The use NSAIDs had uncertain effects on the incidence of AKI compared to placebo. Quality of evidence was very low due to inconsistencies between the two studies. One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group and both of these studies examined much lower doses of NSAIDs than would usually be used for pain relief. NSAIDs may slightly increase serum creatinine (a marker of kidney function which rises in kidney failure) compared with placebo. Quality of evidence was low. These studies only included fit, healthy patients. No reliable conclusions could be drawn from the studies examining urine output due to the different methods of measuring this. It is uncertain whether the use of NSAIDs leads to an increased need for renal replacement therapy (dialysis), more deaths, or increased length of hospital stay.

Conclusions

NSAIDs have uncertain effects on the rates of AKI when used in patients with normal kidney function following surgery. It is uncertain whether NSAIDs increase the need for dialysis. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further studies including patients with other health problems are required.

Authors' conclusions: 

Overall NSAIDs had uncertain effects on the risk of post-operative AKI, may slightly increase post-operative SCr, and it is uncertain whether NSAIDs lead to the need for RRT, death or increases the length of hospital stay. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further larger studies using the Kidney Disease Improving Global Outcomes definition for AKI including patients with co-morbidities are required to confirm these findings. .

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Background: 

Nonsteroidal anti-inflammatory drugs (NSAIDs) provide effective analgesia during the post-operative period but can cause acute kidney injury (AKI) when used peri-operatively (at or around the time of surgery). This is an update of a Cochrane review published in 2007.

Objectives: 

This review looked at the effect of NSAIDs used in the peri-operative period on post-operative kidney function in patients with normal kidney function.

Search strategy: 

We searched Cochrane Kidney and Transplant's Specialised Register to 4 January 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: 

All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the use of NSAIDs versus placebo for the treatment of post-operative pain in patients with normal kidney function were included.

Data collection and analysis: 

Data extraction was carried out independently by two authors as was assessment of risk of bias. Disagreements were resolved by a third author. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). Meta-analyses were used to assess the outcomes of AKI, change in serum creatinine (SCr), urine output, renal replacement therapy (RRT), death (all causes) and length of hospital stay.

Main results: 

We identified 26 studies (8835 participants). Risk of bias was high in 17, unclear in 6and low in three studies. There was high risk of attrition bias in six studies.

Only two studies measured AKI. The use of NSAIDs had uncertain effects on the incidence of AKI compared to placebo (7066 participants: RR 1.79, 95% CI 0.40 to 7.96; I2 = 59%; very low certainty evidence). One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group. Moreover, both of these studies were examining NSAIDs for indications other than analgesia and therefore utilised relatively low doses.

Compared to placebo, NSAIDs may slightly increase serum SCr (15 studies, 794 participants: MD 3.23 μmol/L, 95% CI -0.80 to 7.26; I2 = 63%; low certainty evidence). Studies displayed moderate to high heterogeneity and had multiple exclusion criteria including age and so were not representative of patients undergoing surgery. Three of these studies excluded patients if their creatinine rose post-operatively.

NSAIDs may make little or no difference to post-operative urine output compared to placebo (6 studies, 149 participants: SMD -0.02, 95% CI -0.31 to 0.27). No reliable conclusions could be drawn from these studies due to the differing units of measurements and measurement time points.

It is uncertain whether NSAIDs leads to the need for RRT because the certainty of this evidence is very low (2 studies, 7056 participants: RR 1.57, 95% CI 0.49 to 5.07; I2 = 26%); there were few events and the results were inconsistent.

It is uncertain whether NSAIDs lead to more deaths (2 studies, 312 participants: RR 1.44, 95% CI 0.19 to 11.12; I2 = 38%) or increased the length of hospital stay (3 studies, 410 participants: MD 0.12 days, 95% CI -0.48 to 0.72; I2 = 24%).

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