Rhabdomyolysis and acute renal failure caused by haloperidol-decanoate (neuroleptic malignant syndrome)

A case of rhabomyolysis with attendant severe acute renal failure, arisen in a 59-year-old male treated with haloperidol-decanoate, is presented. The patient has been affected by paranoia schizophrenia since childhood, and he was treated with electroshock and successively with neuroleptics p.o. Four years before our observation, a therapy with haloperidol decanoate (50 mg i.m. monthly) was started. After some time, catatonic like episodes appeared, which got more and more frequent, until they appeared weekly. In occasion of the last of them, he was admitted to our hospital. At the objective examination he presented psychomotory arrest, perspiration, mytacism, severe muscle rigidity, moderate oedems to lower limbs. Laboratory findings showed a pattern consistent with rabdomyolysis and severe renal failure. After that haloperidol decanoate was stopped and rehydration and intensive diuretic therapy was started, the clinical and laboratory pattern went normal, persisting however a light creatinine increase. Probably the rhabdomyolysis was induced by the haloperidol decanoate, and renal failure by secondary severe hyvolemia. This case comes into the so-called neuroleptic malignant syndrome which can rarely arise in patients treated with antipsycotic agents and which causes high mortality, particularly when there are rhabdomyolysis and acute renal failure.     

A case of Satoyoshi syndrome with symptoms resembling neuroleptic malignant syndrome]

Satoyoshi syndrome is a rare neurological disorder of unknown etiology characterized by progressive muscle spasms, alopecia, diarrhea and skeletal abnormalities. We here describe a 25-year-old man who developed symptoms similar to neuroleptic malignant syndrome (NMS). He began to have the clinical characteristics of Satoyoshi syndrome at the age of 12 years. He was admitted to hospitals many times with painful muscle spasms and pyrexia in the early stage of the disease. He received steroid pulse therapy and oral prednisone at the age of 19, the extent and frequency of the spells being reduced thereafter. He was admitted to our hospital due to recurrence of his usual muscle spasms. He was treated with midazolam intravenously to relieve severe muscle ache, pain in the left shoulder, and insomnia. About 90 minutes later, he became comatose, with the following manifestations: hyperthermia, low blood pressure, tachycardia, profuse perspiration, acute respiratory failure, and ensuing cardiac arrest. He developed rhabdomyolysis, acute renal failure, hepatic damage, and diffuse intravascular coagulation. Serum creatine kinase level was elevated to 306,910 IU. He died of multiple organ failure 13 days after admission. His symptoms resembled NMS and malignant hyperthermia (MH). None of patients with Satoyoshi syndrome accompanied by NMS or MH have been reported. It remains to be clarified whether midazolam administration induces NMS in Satoyoshi syndrome. Nevertheless, careful attention should be paid when one administers midazolam to patients with this syndrome.     

Gastrointestinal emergencies with marathon-type running: omental infarction with pancreatitis and liver failure with portal vein thrombosis

This paper reports two patients with catastrophic complications after marathon-type running not hitherto documented. The first, who collapsed with acute abdominal pains, was found at surgery to have infarction of the omentum and later, after a second laparotomy, acute oedematous pancreatitis. The second patient, who collapsed semi-comatose with hyperthermia, developed disseminated intravascular coagulation, rhabdomyolysis, renal shutdown and progressive hepatic failure. With regular dialysis, his condition stabilised but liver function continued to decline, associated with thrombosis of the portal vein. The spectrum of potentially life threatening disorders includes upper gastrointestinal bleeding, haemorrhagic colitis and rarely infarction of the bowel. The present two cases provide further support for ischaemia being a major contributor to the gastrointestinal catastrophes of marathon-type running.     

Activation of coagulation and fibrinolysis in patients with abdominal true aortic aneurysm associated with disseminated intravascular coagulation

Two cases of abdominal true aortic aneurysm (AAA) associated with disseminated intravascular coagulation (DIC) were reported. Case 1 was an 81-year-old male who was admitted because of hematoma on the left leg and in whom was found by MRI an aortic aneurysm of 14 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia, hypofibrinogenemia and increased level of FDP. DIC was well controlled by surgical repair of the aneurysm after the administration of a small dose of heparin. Case 2 was a 60-year-old male who was admitted because of lumbago and hematoemesis and in whom was found by CT and echography an aortic aneurysm of 5.5 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia and an increased level of FDP. On the 2nd hospital day, he suddenly died due to the rupture of the aortic aneurysm. In most of 9 cases with AAA without DIC, plasma levels of thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex and FDP-D dimer were also elevated. These findings indicate that the coagulation and fibrinolysis systems were generally activated in patients with AAA, and that DIC tends to occur in patients with a giant aortic aneurysm or an impending ruptured aneurysm.     

Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura

Serum and urine cytokines were analyzed in children with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Interleukin-6 (IL-6) was elevated in the serum of 33 of 35 children with HUS (94%) and in 2 of 2 children with recurrent TTP. Serum IL-6 was higher in children with HUS who developed anuria, extrarenal manifestations during the acute phase of illness and/or chronic renal sequelae. Tumor necrosis factor-alpha (TNF-alpha) was detected in the serum of 7 patients with HUS (20%) and 1 patient with TTP. IL-6 and TNF-alpha were elevated in the urine of 4 of 4 children with HUS and 2 of 2 children with TTP. Urinary levels were higher than serum levels, suggesting local production of cytokines in the urinary tract. Sequential serum and urine samples showed that IL-6 levels varied with disease activity. IL-6 and TNF-alpha were not detected in the serum (n = 25) and urine (n = 15) of healthy children. We conclude that IL-6 in urine may be used to monitor disease activity in HUS and TTP.     

IL-6 and IL-8 levels in plasma during hematopoietic progenitor transplantation

BACKGROUND AND OBJECTIVE: The relationship between cytokine concentrations and transplant-related complications has been studied in bone marrow transplant patients. The changes in TNF-alpha, IL-1 and IL-6 concentrations after transplantation are well documented in the literature but this is not the case for IL-8. The purpose of the present study was to investigate prospectively the plasma concentration of these cytokines and their relationship to transplant-related complications. DESIGN AND METHODS: Pro-inflammatory cytokine (TNF-alpha, IL-1, IL-6 and IL-8) levels in plasma were determined in a group of 53 patients undergoing hematopoietic progenitor transplantation. Plasma samples were collected weekly from day -7 to day +35 and stored at -70 degrees C until assayed by ELISA. The major transplant-related toxicities registered were: veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infectious episodes, renal failure and mucositis. RESULTS: In spite of the great variability of plasma cytokine profiles between the different patients, we came to various conclusions. Patients' TNF-alpha and IL-1 concentrations correlated well over time. IL-6 and IL-8 profiles were similar and correlated well with febrile episodes. In some cases, an increase in IL-6 preceded hematologic recovery. In our study, increased levels of TNF-alpha, IL-6 and especially IL-8 correlated with hepatic or renal dysfunction as evaluated by increased bilirubin and creatinine in plasma, while pulmonary complications correlated only with increased IL-6 levels. Allogeneic transplant patients had a tendency to have higher TNF-alpha concentrations than autologous transplant patients, probably because an allogeneic transplant is associated with more transplant-related toxicity. Basal disease usually had no effect on cytokine profiles. INTERPRETATION AND CONCLUSIONS: IL-6 and IL-8 were the only cytokines studied whose increase correlated with febrile episodes. High IL-8 values may be a useful predictor of renal dysfunction and pulmonary disease and seems to trigger off high IL-6 levels. Plasma TNF-alpha and IL-1 concentrations during the posttransplant period have not been shown to be predictive of the development of transplant-related complications, and none of the profiles was recognized to be specific for a particular complication in this study.     

Rhabdomyolysis in European viper bite

The case of a child who presented with severe rhabdomyolysis associated with renal failure after a viper bite is reported. Rhabdomyolysis is a serious complication resulting from systemic envenomation and is uncommon after viper bites in Europe. It may be due to oedema, myotoxic agents and haemorrhagic factors and may be responsible for two types of potentially fatal complications, i.e. acute renal failure and hyperkalaemia. The present case highlights the need to investigate routinely for rhabdomyolysis after viper bites. Antivenom therapy is recommended as soon as signs of envenomation are present, without waiting for the onset of complications.     

Prevalence of cervical Chlamydia trachomatis infection in a female population seeking contraception counseling

To analyze the outcome of systemic lupus erythematosus (SLE) associated with acute disseminated intravascular coagulation (DIC) and also to clarify the clinical factor(s) contributing to the outcome, we retrospectively investigated 120 SLE patients treated between 1981 and 1991. Eight of these patients (6.7%) developed acute DIC; four recovered and the other four died within 2 weeks of onset. Infection preceded acute DIC in all these patients. Acute DIC associated with atypical pneumonia was always fatal, while the patients with pharyngitis or urinary tract infection survived when they were treated adequately. Comparison of the dead and surviving groups revealed that the activity of SLE before the onset of DIC, the severity of DIC, and the treatment given for DIC and the coexistent infection were not significantly related to a fatal outcome. However, severe infection such as atypical pneumonia in patients with secondary immunodeficiency was likely to be fatal irrespective of the presence of DIC.     

Fine-needle aspiration biopsy of colonic masses

A 46-year-old-male developed acute renal failure (ARF) secondary to hypokalemic rhabdomyolysis. Potassium supplementation restored renal function following improvement of the rhabdomyolysis. After recovery from ARF, further evaluation disclosed he had hypokalemic metabolic alkalosis, normotensive hyperreninemia, hyperaldosteronism, renal hypomagnesemia, hypocalciuria and hyperplasia of the juxtaglomerular apparatus which are a diagnostic set of disorders in Gitelman's syndrome, a variant of Bartter's syndrome. This is the first reported case of ARF due to hypokalemic rhabdomyolysis associated with Gitelman's syndrome.     

Acute kidney failure in hypothermia

Two cases with acute renal failure after prolonged hypothermia are presented. Both patients were found in come, became rapidly uremic and required hemodilaysis treatment. Although the laboratory findings were typical of severe muscle damage, e.g. elevated levels of serum creatinine phosphokinase, serum lactic dehydrogenase and serum aldolase activities, visible "crush-injuries" were not found. Acute renal failure was characterized by extreme catabolism and severe metabolic acidosis. After 4 and 10 hemodialyses respectively, the patients became polyuric and finally were discharges with normal renal and muscle function. Hypotension with diminished renal perfusion and nontraumatic rhabdomyolysis due to prolonged hypothermia are regarded as the dominant pathogenetic factors in the acute renal failure.     

Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome

OBJECTIVE: To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. DESIGN: Randomized crossover, clinical study. SETTING: University teaching hospital. PATIENTS: Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. INTERVENTION: Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CONCLUSION: CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.     

Acute renal failure in pregnancy

Between 1982 and 1992, 18 cases of pregnancy-related acute renal failure (PR-ARF) were observed (9% of the total number of ARF). Mean age of the women was 32 years (22-40 years). Uterine hemorrhage and preeclampsia/eclampsia were the major causes of ARF, accounting for 61% of the cases. Patchy renal cortical necrosis was suspected in 2 cases whereas signs of disseminated intravascular coagulation (DIC) or microangiopathic hemolytic anemia were present in 6 (33%) and 9 (50%) cases, respectively. Ten women required hemodialysis; and 6 of them, additional plasma exchange sessions. Five patients (28%) died during the acute phase of the illness, mainly due to brain damage, hepatic failure, and sepsis. Among the survivors, a complete (61.5%) or partial recovery (23.1%) was usually seen, but irreversible renal failure was recorded in 2 cases with postpartum hemolytic uremic syndrome (HUS). Short-lasting oligoanuria (< 3 days) represents a good prognostic index. However, the presence of vascular injury (cortical necrosis, HUS) seems to carry a poor prognosis. In conclusion, PR-ARF is still a critical occurrence, associated with serious prognosis for both women and kidneys. So far, the most effective measures remain the careful prevention and the aggressive management of the obstetric complications.     

Neuroleptic malignant syndrome associated with olanzapine

OBJECTIVE: To report a case of neuroleptic malignant syndrome (NMS) associated with the use of olanzapine. CASE SUMMARY: A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic. His only medications were olanzapine 10 mg/d and divalproex sodium 500 mg bid. He was admitted to a hospital and treated for dehydration and mania. Olanzapine was given on 6 of the first 7 hospital days. On hospital day 6, typical NMS developed with the body temperature increasing to 39.9 degrees C, obtundation, rigidity, tremor, diaphoresis, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and elevated serum creatine kinase. Olanzapine was stopped after hospital day 7, and the syndrome resolved by hospital day 12. DISCUSSION: The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness and he received no other drug likely to be associated with the syndrome. This is the first case reported in which NMS was associated with olanzapine.     

Fluid resuscitation and systemic complications in crush syndrome: 14 Hanshin-Awaji earthquake patients

BACKGROUND: Crush syndrome is a form of traumatic rhabdomyolysis characterized by systemic involvement, in which acute renal failure is potentially life-threatening. METHODS: Clinical and laboratory data of 14 crush-syndrome patients transferred to a tertiary emergency department after the Hanshin-Awaji earthquake were analyzed. The patients were buried under collapsed houses for the average of 6.7 +/- 5.7 (SD) hours (range, 1 to 24 hours). They were referred to us 6 to 250 hours after the earthquake. RESULTS: Of those who arrived at our institution within 40 hours, 25% (two of eight) developed renal failure, whereas all six patients who arrived after 40 hours developed renal failure. Peak serum creatine kinase ranged from 6,677 to 134,200 U/L (51,674 +/- 41,776). Renal failure was highly associated with massive muscle damage (serum creatine kinase above 25,000 U/L) and insufficient initial fluid resuscitation (below 10,000 mL/2 days). CONCLUSIONS: Prompt and adequate, if not massive, fluid resuscitation is the key to preventing renal failure after such injury.     

Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure

OBJECTIVE: This study investigates the course of serum cytokine levels in patients with multiple trauma, patients with a ruptured abdominal aortic aneurysm (AAA), and patients undergoing elective AAA repair and the relationship of these cytokines to the development of adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Severe tissue trauma, hemorrhagic shock, and ischemia-reperfusion injury are pathophysiologic mechanisms that may result in an excessive uncontrolled activation of inflammatory cells and mediators. This inflammatory response is thought to play a key role in the development of (remote) cell and organ dysfunction, which is the basis of ARDS and MOF. METHODS: The study concerns 28 patients with multiple trauma, 20 patients admitted in shock because of a ruptured AAA, and 18 patients undergoing elective AAA repair. Arterial blood was serially sampled from admission (or at the start of elective operation) to day 13 in the intensive care unit, and the serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 were determined. RESULTS: Twenty-two patients died, 15 within 48 hours and 7 after several weeks, as a result of ARDS/MOF. At hospital admission and after 6 hours, these nonsurvivors had significantly higher plasma TNF-alpha and IL-1 beta levels than did the survivors. At the same measuring points, TNF-alpha and IL-1 beta were significantly more elevated in patients with ruptured AAA than in traumatized patients. However, IL-6 was significantly higher in the traumatized patients. In 10 patients, ARDS/MOF developed, and 41 had an uncomplicated course in this respect. Those with ARDS/MOF exhibited significantly different cytokine patterns in the early postinjury phase. TNF-alpha and IL-1 beta levels were higher mainly on the first day of admission; IL-6 concentrations were significantly elevated in patients with ARDS/MOF from the second day onward. The latter cytokine showed a good correlation with the daily MOF score during the whole 2-week observation period. CONCLUSIONS: In the early postinjury phase, higher concentrations of these cytokines are associated, not only with an increased mortality rate, but also with an increased risk for subsequent ARDS and MOF. These data therefore support the concept that these syndromes are caused by an overwhelming autodestructive inflammatory response.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

Murine strain differences in the volume effect and incidence of radiation-induced colorectal obstruction

We have previously reported high levels of the coagulation inhibitor TFPI in the blood of patients with gastrointestinal cancer. TFPI is not an acute-phase reactant, but high levels have also been reported in patients with septicaemia and disseminated intravascular coagulation (DIC). To study its relationship with other types of malignancy, TFPI activity was first determined in plasma samples from 214 patients with various malignancies. In a second cohort of 83 patients, total and free TFPI antigen, protein C, antithrombin, fibrin monomer and D-dimer were also measured. Elevated TFPI activity and antigens were found in about half of the patients with solid tumours. In contrast, elevated TFPI was rare in haematological malignancies (12%). In the 18 patients with acute nonlymphocytic leukaemia (ANLL), elevated free TFPI was found only in patients who also had DIC. No correlation was found between TFPI levels and fibrin monomer or D-dimer levels. Only four out of 20 patients with solid tumours had normal levels of fibrin monomer and D-dimer, yet three out of these four had elevated TFPI. In conclusion, elevated TFPI in ANLL is related to the coexistence of DIC. In solid tumour disease increased TFPI may reduce protective fibrin formation, but the pathogenic mechanism is as yet unknown.     

Early release of proinflammatory cytokines after lung transplantation

BACKGROUND: Systemic hypotension may complicate the early postoperative period after lung transplantation. A release of proinflammatory cytokines secondary to lung ischemia/reperfusion injury could be involved in the pathogenesis of this early hemodynamic failure (EHF). Study objective: To assess prospectively whether the occurrence of EHF is associated with a release of cytokines in the systemic circulation. DESIGN: Blood samples were taken daily during the first postoperative week in 26 patients who underwent a double or a single-lung transplantation. These patients were divided into three groups: 7 patients who experienced EHF and subsequently died (EHF group); 15 patients without EHF (control group); and 4 patients without EHF but with an identified sepsis (sepsis group). The serum levels of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 were compared among the three groups. RESULTS: In the EHF group, the levels of each cytokine peaked at day 1 postoperatively. Cytokine levels at day 1 were significantly higher in the EHF group than in the control group (p<0.0006) or in the sepsis group (p<0.003 except for TNF-alpha). CONCLUSION: We conclude that EHF is associated with a massive release of proinflammatory cytokines that could play a determinant role in the pathogenesis of this complication.     

Non-bacterial thrombotic endocarditis: clinicopathologic correlations

Sixty-five cases of nonbacterial thrombotic endocarditis (NBTE) were discovered at autopsy during a 10 year period--an incidence of 1.6 per cent in the adult autopsy population. In 51 cases, one or more malignant neoplasms were associated; adenocarcinoma represented the most frequent histologic type of related neoplasm. Coagulation abnormalities suggestive of disseminated intravascular coagulation (DIC) were present in 18.5 per cent of the cases. It is possible that both the valvular and peripheral intravascular thromboses in at least some cases of NBTE represent the abnormal coagulation of DIC. Arterial thrombosis with infarction occurred in many peripheral organs. Splenic and renal were most frequent, but cerebral and cardiac consequences were the most significant.