Hemoperitoneum from rupture of liver subcapsular hematoma after laparoscopic cholecystectomy attributed to ketorolac. Report of a case

Ketorolac is one of the most common nonsteroidal anti-inflammatory drugs used to control postoperative pain. However, peri- and postoperative administration of ketorolac is associated with an increased risk of gastrointestinal bleeding as described in the literature. Notwithstanding this event is not frequent, it can expose the patient to serious complications that should be quickly recognised and effectively treated. We present a report about a female patient with cholelithiasis who underwent a laparoscopic cholecystectomy. After the operation, the patient had a haemorrhage that we attributed to surgery in a first time and then to administration of ketorolac.     

Acute perioperative pain in neonates: An evidence-based review of neurophysiology and management

Current literature lacks systematic data on acute perioperative pain management in neonates and mainly focuses only on procedural pain management. In the current review, the neurophysiological basis of neonatal pain perception and the role of different analgesic drugs and techniques in perioperative pain management in neonates are systematically reviewed. Intravenous opioids such as morphine or fentanyl as either intermittent bolus or continuous infusion remain the most common modality for the treatment of perioperative pain. Paracetamol has a promising role in decreasing opioid requirement. However, routine use of ketorolac or other nonsteroidal anti-inflammatory drugs is not usually recommended. Epidural analgesia is safe in experienced hands and provides several benefits over systemic opioids such as early extubation and early return of bowel function.     

Genitourinary complications of sickle cell disease

PURPOSE: In the last half century the molecular biology, pathophysiology and natural history of sickle cell disease have been well defined. Sickle cell disease causes microvascular occlusion, which is manifested in most organ systems. The genitourinary tract is most commonly affected by hematuria, urinary tract infection and priapism but other more serious sequelae have been identified. MATERIALS AND METHODS: We performed a computerized MEDLINE search from 1965 to the present and a bibliographic review of cross references. These references were analyzed for meaningful findings and case reports. RESULTS: The diagnosis and management of sickle cell disease have advanced rapidly with a significant increase in the life expectancy of affected patients and recognition of a greater number of genitourinary complications. Renal function may be mildly altered or lost completely. Patients with sickle cell disease are at increased risk for urinary tract infection. Priapism is a painful complication of sickle cell disease that is poorly understood and challenging to treat and prevent. Testicular infarction has also been noted. Furthermore, renal medullary carcinoma, a highly lethal tumor, develops almost exclusively in young patients with sickle cell trait. CONCLUSIONS: Heightened awareness of the genitourinary complications of sickle cell disease may prevent end stage disease, including renal failure and impotence. New forms of therapy for sickle cell disease, such as hydroxyurea, may prevent these complications in the future.     

Urinary retention in sickle cell syndromes

Four patients with sickle cell disease noted the development of urinary retention during an acute painful crisis. The acute urinary retention resolved with improvement in the painful sickle cell crisis. No evidence of anatomic urologic defect, systemic neurologic abnormality, or infection was documented in these patients. Patients with sickle cell disease in painful crisis should be observed for signs of acute urinary retention.     

Renal amyloidosis in a child with sickle cell anemia

The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.     

Acute renal failure, associated with non-steroidal anti-inflammatory drugs in healthy children

Seven patients aged 13 to 17.5 years developed acute renal failure after treatment with a variety of non-steroidal anti-inflammatory drugs (NSAID): naproxen, diclofenac, ibuprofen, dipyrone and paracetamol. Six of the patients used more than one kind of NSAID. None of the patients had previous history of renal disease or concomitant treatment with other drugs. The time interval between NSAID administration to the emergence of symptoms ranged from 1 to 4 days. The most common presenting symptoms were flank pain (4 patients), abdominal pain (3 patients) and vomiting (3 patients). All patients had normal urine output. Microscopic hematuria and proteinuria were found in 5 patients and leukocyturia in 2. Serum creatinine ranged from 1.3 to 8.3 mg% at presentation. Kidney biopsy was performed in 3 patients and showed findings consistent with mild interstitial inflammation in 1 patient, and normal renal tissue in 2. All patients were treated with intravenous fluids, 1 received corticosteroids. Renal function completely normalized in all patients within 7 to 16 days.     

Safety of ketorolac in neonates and infants after cardiac surgery

BACKGROUND: Ketorolac is an injectable nonsteroidal anti-inflammatory drug that is often used as a transitional short-term analgesic to treat moderate pain and to decrease opioid use. There is a paucity of literature documenting the safety of using ketorolac in neonates and infants after cardiac surgery. METHODS: A retrospective chart review was performed which identified all patients <6 months of age who received ketorolac after cardiac surgery. Patients' demographic, surgical, and dosing data were collected. A Student's t-test was used to identify significant differences in renal and hematologic laboratory values at baseline and at 48 h of treatment. RESULTS: A total of 53 children <6 months of age received at least one dose of ketorolac after cardiac surgery. Eleven of 53 children (21%) were <1 month of age. The blood urea nitrogen/serum creatinine (SCr) levels increased from baseline at 48 h of therapy in all infants, but stayed within normal limits. The largest increase in SCr level from baseline on any day of ketorolac therapy was 26 micromol x l(-1) (0.3 mg x dl(-1)) which occurred in two neonates. Four patients (three infants and one neonate) had minor episodes of bleeding while being treated with ketorolac. There were no clinically significant changes in hemoglobin, hematocrit or platelet count. None of these episodes caused hemodynamic instability nor required transfusion of blood products. CONCLUSIONS: Ketorolac was used safely in neonates and infants who have had cardiac surgery at our institution. Ketorolac was not associated with any adverse hematologic or renal effects. Prospective investigation is warranted to further assess the safety and effectiveness of ketorolac in this patient population.     

Pretreatment with ketorolac and venous occlusion to reduce pain on injection of propofol

We performed a randomised, double-blind, prospective trial to discover whether intravenous ketorolac 10 mg made up to 2 ml with saline, with or without venous occlusion for 2 min, reduces the pain on injection of propofol. In 90 patients, pain scores were obtained during injection of propofol following pretreatment of the vein with saline, ketorolac or ketorolac with venous occlusion. Pain on injection of ketorolac was more common than with saline (p = 0.02). The incidence of severe pain following propofol was reduced by ketorolac with venous occlusion (p = 0.019) compared with saline or ketorolac without venous occlusion. There was no difference in venous sequelae at 7 days postoperatively between the groups. Our results suggest that pain on injection of propofol may be related to release of local kininogens and that nonsteroidal anti-inflammatory drugs may have a role in reducing that pain.     

Recurrent sickle cell nephropathy in a transplanted kidney

Of patients who developed end-stage renal disease secondary to sickle cell anemia (SCA), some have undergone renal transplantation with reasonable success. We recently cared for a patient with SCA and a functioning, transplanted kidney who experienced a permanent decline in renal function three and one-half years following transplant. The evaluation of his renal dysfunction revealed multiple features to support recurrence of sickle cell nephropathy as the cause for the deterioration.     

Acute colonic pseudoobstruction in a child with sickle cell disease treated with neostigmine

Sickle cell disease is a disorder that produces significant morbidity and mortality. Vaso-occlusive pain crises are the most common presenting symptom associated with sickle cell patients. A rare, yet important to recognize, complication of sickle cell disease is acute colonic pseudoobstruction, also known as Ogilvie's syndrome. These patients may present with symptoms that are difficult to distinguish from other etiologies of abdominal pain, but a thorough diagnostic workup can provide important clues. Furthermore, there is no agreement on optimal treatment of pseudoobstruction. We report the first pediatric case of acute pseudoobstruction secondary to sickle cell disease that was treated successfully with neostigmine. Early recognition of this phenomenon is important as it alters patient management, can be treated medically, and may avoid unnecessary surgical intervention.     

Rapid loss of renal parenchyma after acute obstruction

Urinary tract obstruction (UTO) is a frequent cause of renal failure in the pediatric population. We report a patient with type I/I cystinuria, followed prospectively from birth with yearly ultrasonography, who developed acute UTO due to a cystine stone at 10 years of age. In animal models of UTO, acute obstruction produces rapid loss of renal parenchyma secondary to apoptosis of tubular cells. Since we had prospectively obtained serial ultrasonographic measurements of renal growth, we were able to document sudden decrease in kidney size and function following UTO, suggesting that programmed cell death may similarly have caused the rapid irreversible loss of renal parenchyma in our patient. Despite surgical relief of the obstruction, kidney size decreased for at least 3–4 months. We speculate that anti-apoptotic drugs might be considered as a therapeutic strategy to protect ongoing renal parenchyma loss in UTO. Received: 26 April 2001 / Revised: 28 June 2001 / Accepted: 29 June 2001     

Reversible renal failure associated with ibuprofen in a child. A case report

The clinical presentation and management of a young boy with acute non-oliguric renal failure associated with a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, prescribed for the relief of pain is described. Deterioration of renal function developed unexpectedly but fortunately withdrawal of the drug and appropriate management resulted in spontaneous recovery. All NSAIDs have the ability to interfere with renal function and their administration should probably be avoided in children with pre-existing dehydration or with conditions that predispose to an increased risk of renal insufficiency.     

Methylprednisolone and ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds

BACKGROUND: Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) decrease acute postoperative pain and hyperalgesia. The objectives of this study were to investigate the effects of methylprednisolone and ketorolac on hyperalgesia around a skin burn injury and on pressure pain thresholds. METHODS: In a double-blind, placebo-controlled, randomized trial with cross-over design, methylprednisolone 125 mg, ketorolac 60 mg or placebo was administered intravenously in 12 male volunteers on three separate days at least 4 days apart. Primary and secondary hyperalgesia were produced by a first-degree burn injury on abdominal skin 45 min before injection of the test medicines. The area of secondary mechanical hyperalgesia outside the site of injury was measured. Pressure pain stimuli were applied on the base of a fingernail, increasing until the pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPTT) were reached. RESULTS: Compared with placebo, the active drugs reduced the area of secondary hyperalgesia (methylprednisolone, P < 0.001; ketorolac, P < 0.01). Ketorolac but not methylprednisolone increased PPDT compared with placebo (P < 0.05). Both active drugs increased PPTT compared with placebo (methylprednisolone, P < 0.01; ketorolac, P < 0.001). Ketorolac increased PPTT more than methylprednisolone (P < 0.05). CONCLUSIONS: Methylprednisolone and ketorolac increased PPTT attenuated secondary hyperalgesia around a skin burn injury. PPTT increased after both methylprednisolone and ketorolac. The present study demonstrates analgesic and anti-hyperalgesic properties of a glucocorticoid and a non-selective NSAID that have not been demonstrated previously in human subjects.     

Acute splenic sequestration crisis in sickle cell disease: early detection and treatment.

Acute splenic sequestration crisis (ASSC) in children with various forms of sickle cell disease can result in life-threatening circulatory collapse due to the loss of circulating blood volume. Over a 6-year period we have treated 12 patients ranging in age from 5 1/2 months to 7 years presenting with acute sequestration crisis. Eleven had homozygous sickle cell disease and the other had sickle-thalassemia. One patient died of acute circulatory collapse. Eight patients underwent splenectomy after a major episode of sequestration with no serious infectious complications up to 5 years following splenectomy. Three patients with minor episodes have been followed with no recurrences. To foster early detection of this potentially lethal complication of sickle cell disease, an educational program in our Comprehensive Sickle Cell Center instructs the parents to examine the spleen and bring their child in for evaluation if the spleen enlarges. A newly developed videotape describes the common symptoms of ASSC and illustrates the technique of palpating the spleen. With early detection of sickle cell disease by neonatal screening and the educational program, the morbidity and mortality from this complication of sickle cell disease can be reduced.     

A double-blind placebo-controlled comparison of a novel formulation of intravenous diclofenac and ketorolac for postoperative third molar extraction pain

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N = 51 for all groups, except N = 47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P = .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.     

Perioperative management in children with sickle cell disease undergoing laparoscopic surgery.

OBJECTIVE: The aim of this study was to evaluate our experience with laparoscopic surgery in children with sickle cell disease. METHODS: A retrospective chart review was performed to analyze the indication for surgery, perioperative management, surgical technique, complications, duration of hospitalization, and outcome. One pediatric surgeon performed all procedures. RESULTS: Thirteen children underwent laparoscopic surgery for the following indications: symptomatic cholelithiasis/cholecystitis in 9; recurrent splenic sequestration in 3; and hypersplenism/symptomatic cholelithiasis in 1. The 7 boys and 6 girls had a median age of 7.8 years. Patients undergoing splenectomy only were younger than those undergoing cholecystectomy (median age, 3.6 years versus 11.5 years, respectively). Four children underwent endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy because of common bile duct dilatation and stones. Twelve patients received packed red blood cell transfusions prior to surgery. The median operative time was 150 minutes, and the median hospitalization was 3 days. Four patients suffered postoperative complications (2 with acute chest syndrome, 1 with recurrent abdominal pain, and 1 with priapism). The patient with abdominal pain was found to have a retained stone in the common bile duct, which was retrieved via endoscopic retrograde cholangiopancreatography and sphincterotomy. All complications resolved with medical management. CONCLUSIONS: Laparoscopic surgery is safe in children with sickle cell disease. Meticulous attention to perioperative management, transfusion guidelines, and pulmonary care may decrease the incidence of acute chest syndrome.     

Combined liver and kidney transplantation in a patient with sickle cell disease

Sickle cell intrahepatic cholestasis is a potentially fatal end-organ complication of sickle cell anemia. Renal involvement in sickle cell anemia is common, and in some cases, can present as acute renal failure. Although renal transplants have been performed in patients with sickle cell anemia since the late 1960s and a number of liver transplants have been recently performed for these complications, there has not been experience with dual organ transplantation for sickle cell anemia-related complications. We describe the case of a patient with sickle cell anemia who underwent successful combined liver and kidney transplantation after the development of acute sickle cell intrahepatic cholestasis and renal failure requiring continuous venovenous hemodialysis. The patient underwent a successful combined liver and kidney transplant with limited perioperative complications and preserved allograft function. At 22 months posttransplant, the patient expired as a result of an acute pulmonary embolus in the setting of bilateral hip fractures. Autopsy revealed no evidence of liver or kidney allograft rejection and evidence of chronic sickle cell nephropathy in the native kidney. Combined liver and kidney transplantation is a viable therapeutic option in patients with severe end-organ effects of sickle cell anemia.     

Immunotactoid glomerulopathy in sickle cell anemia

A 12-year-old African American male with homozygous sickle cell disease (SCD) was admitted with insidious onset of periorbital and scrotal edema. The initial evaluation failed to reveal any underlying monoclonal gammopathy, or cryoglobulinemia, or other systemic causes for the renal disease. A percutaneous renal biopsy was consistent with immunotactoid glomerulopathy (ITG), which is rare in children and is characterized histologically by fibrillar deposits in the glomeruli. Children can present with symptoms of nephrotic syndrome and progress to end stage renal disease. Our patient was treated with an ACE inhibitor and is currently free of edema and with normal renal function on follow-up at 1 year. Immunotactoid glomerulopathy should be considered in the differential diagnosis of nephrotic syndrome in children with sickle cell disease. Renal biopsy is indicated in children with sickle cell disease and nephrotic syndrome and ITG should be considered as potential cause. Although there is no effective treatment for this condition, ACE inhibitors can decrease the proteinuria and possibly delay the progression to end stage renal disease. The side effects related to the use of ACE inhibitors should be monitored. These include renal impairment, hyperkalemia, anemia, neutropenia, and angioedema. Since we have a short follow-up in our patient, the role and safety of ACE inhibitors in the management of ITG need further evaluation. Received: 4 February 2000 / Revised: 3 July 2000 / Accepted: 19 July 2000     

A nontransfusional perioperative management regimen for patients with sickle cell disease undergoing laparoscopic cholecystectomy

BACKGROUND: Patients with sickle cell disease (SCD) are at increased risk for cholelithiasis. Laparoscopic cholecystectomy is the most frequent general surgical operation performed for this group of patients. Acute chest syndrome (ACS) is the most common cause of postoperative death among SCD patients. This study aimed to evaluate the impact of a novel perioperative management regimen involving prophylactic continuous positive airways pressure (CPAP) ventilation and avoidance of preoperative blood transfusion on postoperative SCD-related complications after laparoscopic cholecystectomy. METHODS: A retrospective study included all SCD patients who underwent laparoscopic cholecystectomy since 1997 at our institution. Medical notes were analyzed to assess the rates of postoperative complications in relation to the severity of SCD. RESULTS: A total of 13 patients were identified. There were no recorded episodes of acute painful crises and only one patient experienced an episode of ACS requiring protracted CPAP. CONCLUSION: Laparoscopic cholecystectomy can be safely performed for SCD patients without prior blood transfusion. A defined perioperative regimen including the use of routine postoperative prophylactic CPAP for these patients helps to reduce SCD-related postoperative complications such as ACS and painful vaso-occlusive crises.     

Ketorolac: safe and effective analgesia for the management of renal cortical tumors with partial nephrectomy

PURPOSE: Ketorolac has demonstrated advantages as a supplement to opioid based analgesia in several surgical settings, including donor nephrectomy. To our knowledge there has been no published data to date on the use of ketorolac in patients undergoing partial nephrectomy. We compared analgesia with ketorolac and opioids to analgesia with opioids alone with regard to pain control, postoperative recovery and effects on renal function in patients with renal cortical tumors surgically managed by partial nephrectomy. MATERIALS AND METHODS: Records for 154 patients treated with partial nephrectomy for renal cortical tumors were retrospectively analyzed. Clinicopathological variables examined were age, gender, medication use, comorbidity profile, operation side, estimated blood loss, hospital stay, operative duration, American Society of Anesthesiologists class, histopathology results, perioperative transfusion status, ischemia type (warm vs cold vs none), duration of renal artery cross clamping, tumor size and intraparenchymal location, pathological stage and perioperative complications. Postoperative duration to the initiation of solid diet, discontinuation of patient controlled analgesia and overall pain control were assessed. Serum creatinine was measured during the preoperative period, and at 1, 3 or greater and 30 or greater days postoperatively. RESULTS: Patients who received ketorolac demonstrated superior postoperative recovery with an earlier return to solid diet and earlier discontinuation of patient controlled analgesia. Treatment groups were similar with respect to changes in serum creatinine, blood loss, transfusion rates and complication rates. Ketorolac was not associated with an increased risk of acute renal failure. CONCLUSIONS: Ketorolac is a safe and effective supplement to opioid based analgesia for pain control after partial nephrectomy.