|Year : 2014 | Volume
| Issue : 3 | Page : 359-361
Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient
Arup K Misra, Satish E Bahekar, Ranjana S Kale, Sushil K Varma
Department of Pharmacology, MGIMS, Sevagram, Maharashtra, India
|Date of Web Publication||18-Mar-2014|
Satish E Bahekar
Department of Pharmacology, Mahatma Gandhi Institute of Medical Sciences, Sewagram - 442 102, Maharashtra
Source of Support: None, Conflict of Interest: None
Acute renal failure is a life threatening condition. Nonsteroidal antiinflammatory drugs (NSAIDs) and cephalosporins are widely used postoperative drugs. NSAID-induced acute renal failure has been reported in the past. In this case, drug interaction and decompensated state of the patient precipitate the condition. NSAIDs inhibit prostaglandins synthesis and thus aggravate ischemia to the kidney that is already facing volume crisis due to surgery. Due to renal dysfunction, plasma ceftriaxone level increases due to decrease clearance and it also acts as nephrotoxic by unknown mechanism. On the other hand, ceftriaxone on its interaction with diclofenac for renal tubular clearance also increases the level of diclofenac and thus further aggravate the ischemia. It is a reversible condition with excluding diclofenac from the treatment regimen and giving adequate hydration to the patient. This highlights the importance of hydration and knowledge of drugs interactions in a postsurgical patient.
Keywords: Drug interaction, ischemia, prostaglandins, volume depletion
|How to cite this article:|
Misra AK, Bahekar SE, Kale RS, Varma SK. Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient. Med J DY Patil Univ 2014;7:359-61
|How to cite this URL:|
Misra AK, Bahekar SE, Kale RS, Varma SK. Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient. Med J DY Patil Univ [serial online] 2014 [cited 2020 Jun 2];7:359-61. Available from: http://www.mjdrdypu.org/text.asp?2014/7/3/359/128983
| Introduction|| |
Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics are the most clinically used drugs for postoperative patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known analgesic and anti-inflammatory used for mild to moderate postoperative pain.  On the other hand, third-generation cephalosporins without any limitations and rationality are used for prophylaxis in the surgical procedures without any knowledge of the flora involved.  Ceftriaxone has been implicated in renal dysfunction when it is added with another nephrotoxic drug.  On the other hand, NSAIDs are the well-known drugs accounting for about 15% of drug-induced acute renal failure.  We would like to report a case of drug-interaction-induced acute renal failure that was favored by the presence of falling renal function and drug interaction.
| Case report|| |
A 40-year-old female patient, a case of irreducible hernia, was admitted and operated for repair. The operative procedure was uneventful. After surgery, she was prescribed combination of injection ceftriaxone and sulbactam 1.5 gm intravenous (i.v.), injection diclofenac sodium 75 mg intramuscular (i.m.), and injection ranitidine 150 mg (i.v) thrice a day, respectively. On the second postoperative day, she started complaining of decrease urine output with difficulty in breathing. On examination, her air entry, bilaterally, was decreased on auscultation and her oxygen saturation (SPO2) was around 70%. On second postoperative day, she was given injection Furosemide 40 mg (i.v) once a day but other medications were continued. On the third postoperative day, her urine output was almost negligible. Her antibiotic and analgesic were replaced by combination of injections piperacillin and tazobactam 2.25 gm (i.v) twice a day and injection tramadol 50 mg (i.m.) twice a day. On examination, the patient was alert and her pulse and blood pressure were within normal limits. She had no pallor, icterus, lymphadenopathy, or clubbing but she had pedal edema. Her cardiovascular and central nervous systems were within normal limits.
On investigating, it was found that her plasma creatinine, urea, and potassium were raised to 3.80 mg/dl (normal 0.1-1 mg/dl), 71 mg/dl (normal 20-40 mg/dl) and 5.9 mEq/L (normal 3.5-5 mEq/L), respectively, on the third postoperative day. The tests done prior to surgery and after are shown in [Table 1]. Urinary sodium was decreased 12.6 mEq/L (normal 25-50 mEq/L) and so the osmolality to 54.3 mEq/L (normal values 100-260 mEq/L). Her complete blood counts showed increase in the leucocytes count and decrease in platelet count.
|Table 1: Values of biochemical parameters in pre- and|
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Following the deranged report, injection diclofenac and combination of injection ceftriaxone and sulbactam were stopped and other medications were continued; her investigations were repeated the following day [Table 1]. Her plasma creatinine and urea levels did not show significant change on the following day, however, on day 7 the values started to drop toward normality with plasma creatinine 2.9 mg/dl, urea 51 mg/dl, potassium 4.9 mEq/L, and sodium 132 mEq/L with increase in urine output. Her pedal edema was also subsiding with improvement in breathing. Her complete blood counts also showed improvement in leucocytes counts and increase in platelets count. Her parameters are planned for further evaluation in her follow-up visit.
| Discussion|| |
Acute renal failure is a frequent complication following surgical procedures and in critically ill patients. It accounts for major cause of mortality despite the use of pharmacologic agents.  During surgery, renal blood flow is reduced by almost 30%. Prostaglandin has vasodilatory effects on renal vascular bed and enhances blood flow from renal cortex to nephrons, and thus helps in maintaining the glomerular filtration rate (GFR).  Prostaglandins as such have no major role in normal subject but when it is inhibited in subjects who require prostaglandin for maintenance of renal blood flow, fluid and electrolyte homeostasis, its inhibition may have profound adverse renal effects. NSAIDs are well-known renal toxins that alter renal function by inhibiting protective renal prostaglandins that leads to reversible renal ischemia.  The consequences of NSAID-induced renal function may lead to salt and water retention, edema and hyperkalemia due to effects on rennin, and aldosterone secretion. , On the other hand, ceftriaxone also acts as a nephrotoxic agent if added with another nephrotoxic agents.  Due to the decreased GFR, there is decreased elimination of ceftriaxone in surgical intensive care patients due to acute renal failure that may lead to the increase of ceftriaxone in plasma and might precipitate toxic effects on kidney by unknown mechanism. , The decrease in renal function may cause threefold increase in half life, 50% reduction in volume distribution, and halved clearance of ceftriaxone and vice versa, ceftriaxone will also increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. These deranged pharmacokinetics parameters may lead to unsuspected accumulation of drugs in renal dysfunction patients. 
In this case, the patient had normal renal functions before the surgery. She is neither hypertensive nor diabetic. Due to surgery, there is decline in renal blood flow and on addition of injection furesemide on the second postoperative day to increase the urine output there were chances that the patient may land into volume depletion. Due to volume depletion, there were more chances of renal ischemia by NSAIDs which may further deteriorate the symptoms and deranged the biochemical parameters.  Though, the patient's vitals were within normal limits but there was marked reduction in urine on the second day of the operation leading to the anuric state on the third day, following the addition of injection furosemide and with continuation of NSAIDs. The pedal edema was also increased with sudden rise of plasma creatinine, urea, and potassium. With low urine output, her urine analysis also showed low urine sodium and low osmolality that signifies renal dysfunction to concentrate urine.
In this patient, injection diclofenac sodium 75 mg, three times a day (225 mg/day), was given in higher dose that is more than the normal limit of 150 mg/day that might be the precipitating factor in inducing acute renal failure  in combination of injection ceftriaxone. The symptoms are further precipitated with the addition of injection furosemide that further causes volume deletion. According to Naranjo's adverse drug reaction probability scale, both the drugs are the probable cause of this hemodynamically induced acute renal failure.  As was mentioned in the case report that after discontinuing diclofenac and ceftriaxone there was improvement in patient's symptoms and electrolytes, the renal toxicity of diclofenac and ceftriaxone in combination confirms.
NSAID-induced acute renal failure in volume-depleted patients is reversible and can be avoided by removing or replacing NSAIDs with another analgesic. On the other hand, ceftriaxone can be replaced by an antibiotic that is not depended on renal clearance or it can be continued by lowering its dose according to creatinine clearance if other analgesics (other than renal toxic NSAIDs) are used. In these conditions, renal sparing NSAIDs (nonselective or coxibs) can be preferred. Adequate hydration of the patient should be maintained with restriction of the dietary salts.
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