Can phenformin-induced lactic acidosis be prevented?

Although patients taking phenformin are more likely to develop lactic acidosis in the presence of renal, cardiovascular, or hepatic disease, criteria for safe use of the drug are not well established. Eight diabetics died of lactic acidosis in Nottingham in 1972-5 and all were taking phenformin in therapeutic doses. Six had attended the diabetic clinic within a month of their terminal illness. Two patients had appreciable renal impairment and should not have been given phenformin. Four had hypertension and minimal evidence of renal disease, while in two no predisposing factor was identified. There are so many contraindications to the use of phenformin that it is doubtful whether patients on the drug can be monitored adequately. We suggest that phenformin should be withdrawn from general use.     

Pancreatitis and severe metabolic abnormalities due to phenformin therapy

Two elderly diabetic patients with abdominal pain were demonstrated to have complications of phenformin hydrochloride therapy. The first developed severe lactic acidosis treated with sodium bicarbonate given intravenously and followed by rebound alkalosis. The second showed severe acidosis (specimens for lactate determination were unfortunately unsatisfactory for analysis) and similar alkalotic rebound after therapy. She then developed severe pancreatitis, proved at operation, no cause for which other than phenformin was apparent. Poor renal and hepatic function predispose to these conditions by increasing serum phenformin levels and by decreasing urinary excretion of its metabolites. The acidosis should be treated judiciously with sodium bicarbonate administered intravenously. A rebound alkalosis, ensuring as the accumulated lactate is metabolized, is best treated by potassium chloride and ammonium chloride given intravenously. The mechanism by which phenformin causes pancreatitis is unknown, but termination of therapy causes cessation of the pancreatitis.     

Phenformin-associated lactic acidosis due to imported phenformin

OBJECTIVE: To emphasize the continued incidence of phenformin-associated lactic acidosis. CASE REPORT: We report a case of phenformin-associated lactic acidosis in a Chinese man who received phenformin while in China. Diagnosis was made; the patient was treated appropriately and survived. COMMENTS: Phenformin-associated lactic acidosis may still occur in the U.S.     

Phenformin and hyperamylasemia in lactic acidosis

All cases of lactic acidosis occurring during a 23-month period in a metropolitan teaching hospital were reviewed to ascertain the frequency of hyperamylasemia. Serum amylase activity had been measured in 12 of 26 patients and was elevated in eight (67%). Hyperamylasemia was not significantly more frequent in patients with phenformin-associated lactic acidosis than in patients with lactic acidosis who had not received phenformin. Serum amylase activity did not correlate with the severity of acidosis (arterial pH) or with renal function (serum creatinine).     

Gender differences in kappa-opioid modulation of cocaine-induced behavior and NMDA-evoked dopamine release

CASE REPORT: An 18-year-old female who accidentally ingested strychnine developed chemical pancreatitis in addition to the classical clinical picture of strychnine poisoning. Many drugs or chemicals have been reported to be associated with pancreatitis; however, this paper provides us with the first evidence that acute pancreatitis may follow strychnine poisoning. The patient survived despite the development of seizures, lactic acidosis, rhabdomyolysis, and pulmonary infiltrates. Toxicology testing confirmed the presence of strychnine in blood (2.17 mg/L), gastric aspirate, and urine. Attention is drawn to the fact that survival can follow the ingestion of large doses of strychnine providing there is no delay in diagnosis and treatment. The pathophysiologic mechanism of chemical pancreatitis is discussed.     

Nervous stimulation of gastrin release

We report 18 consecutive phenformin-treated diabetic patients admitted to this Medical Service acutely ill with metabolic acidosis. Lactic acidosis was anticipated, and documented, in all. Also, however, though most of the patients had only weakly positive, or even negative, serum reactions with the nitroprusside reagent, all were found to have coexisting ketoacidosis, plasma 3-hydroxybutyrate averaging 7.1 mmol/L. +/- 3.9 (S.D.). This finding suggest that treatment of these patients should include insulin, and often also glucose, because most do not have marked hyperglycemia and some have hypoglycemia. The lactic acidosis in the nine patients who survivied was, on average, less severe than in the nine who died, but the difference was not statistically significant. Surivival correlated closely with the absence of shock on arrival. Only eight patients had a identifiable acute illness other than the metabolic acidosis. The other 10 patients had no discernible cause for the acute illness apart from their treatment with phenoformin. This finding raises serious doubts about whether phenformin should be used to treat patients with diabetes.     

Acute pancreatitis associated with the use of lisinopril

OBJECTIVE: To report a case of acute pancreatitis associated with lisinopril use. CASE SUMMARY: A 67-year-old man with no past history of pancreatitis or its associated risk factors developed acute pancreatitis after taking lisinopril for two years. To date, the use of angiotensin-converting enzyme (ACE) inhibitors and development of pancreatitis has been described in the literature with captopril, enalapril maleate, and one case temporally related to lisinopril use. CONCLUSIONS: The use of ACE inhibitors as first-line agents in controlling hypertension and congestive heart failure has increased. In addition to monitoring for efficacy and commonly reported adverse effects, clinicians need to be aware that acute pancreatitis may occur with all ACE inhibitors.     

Apropos of a case of acute pancreatitis revealing cystic dilatation of the common bile duct

Dilatation of the common bile duct is rarely caused by cystic formations. Though the pathogenesis is uncertain, congenital disorders have been suggested. Most cases are observed in small children (80% female predominance) with only 20% of the cases reported in adults. Clinical signs vary. Recurrent acute pancreatitis has been reported but is rare. New imaging techniques using CT-scan cholangiography and sometimes MR cholangiography have greatly improved the diagnostic approach. MR of the bile ducts is a recent noninvasive technique enabling an analysis of the biliopancreatic ducts without contrast injection into the bile. To our knowledge, cystic dilatation of the common bile duct has not been previously reported in the literature. We report an interesting case in a 25-year-old woman who developed an episode of acute pancreatitis during the post partum period. We describe the clinical aspects and the different imaging findings, including magnetic resonance cholangiography results.     

The promise and risk of a new technology: the Lehigh Valley Hospital''s experience with liquid-based cervical cytology

We report the case of a 28-year-old woman who presented with two episodes of acute pancreatitis 3 years apart both of which were complicated by the development of thrombotic thrombocytopenic purpura (TTP). On each occasion the TTP was successfully managed with plasmapheresis. Although TTP has been reported as causing acute pancreatitis, the induction of TTP by pancreatitis is rare. As far as we are aware this is the first reported case of recurrent TTP in association with acute pancreatitis. It is possible that circulating pancreatic proteases may have induced the TTP by modifying von Willebrand factor enabling spontaneous platelet membrane receptor binding resulting in intravascular platelet aggregation.     

Epinephrine-induced lactic acidosis following cardiopulmonary bypass

OBJECTIVE: To determine if lactic acidosis occurring after cardiopulmonary bypass could be attributed to the metabolic or other effects of epinephrine administration. DESIGN: Prospective, randomized study. SETTING: Postsurgical cardiothoracic intensive therapy unit. PATIENTS: Thirty-six adult patients, without acidosis, requiring vasoconstrictors for the management of hypotension after cardiopulmonary bypass. INTERVENTIONS: Randomized administration of either epinephrine or norepinephrine by infusion. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and metabolic data were collected before commencement of vasoconstrictor therapy (time 0) and then 1 hr (time 1), 6 to 10 hrs (time 2), and 22 to 30 hrs (time 3) later. Six of the 19 patients who received epinephrine developed lactic acidosis. None of the 17 patients receiving norepinephrine developed lactic acidosis. In the epinephrine group, but not in the norepinephrine group, lactate concentration increased significantly at times 1 and 2 (p = .01), while pH and base excess decreased (p < or = .01). Blood glucose concentration was higher in the epinephrine group at time 2 (p = .02), while the cardiac index (p < .03) and the mixed venous Po2 (p = .04) were higher at time 1. compared with the norepinephrine group, the patients receiving epinephrine had higher femoral venous lactate concentrations (p = .03), increased lower limb blood flow (p = .05), and increased femoral venous oxygen saturations (p = .04). CONCLUSIONS: The use of epinephrine after cardiopulmonary bypass precipitates the development of lactic acidosis in some patients. This phenomenon is presumably a beta-mediated effect, and is associated with an increase in whole-body and lower limb blood flow and a decrease in whole-body and transfemoral oxygen extraction. The phenomenon does not appear to be related to reduced tissue perfusion and does not have the poor outlook of lactic acidosis associated with shock.     

Can amiodarone pulmonary toxicity be predicted in patients undergoing implantable cardioverter defibrillator implantation?

Implantable cardioverter defibrillator (ICD) implantation is rapidly becoming accepted as primary therapy for malignant ventricular arrhythmias. Many patients undergoing ICD implantation are on concomitant antiarrhythmic drugs to decrease shock frequency, slow tachycardia rate, and suppress supraventricular arrhythmias. Amiodarone is a potent antiarrhythmic agent that is also frequently used in the treatment of patients with refractory ventricular arrhythmias. Ten to forty percent of patients undergoing ICD implantation will also be taking amiodarone. It has been reported to cause pulmonary toxicity in about 5% of patients per year. Acute amiodarone toxicity presenting as adult respiratory distress syndrome has been reported much less frequently. Although perioperative morbidity due to amiodarone has been described, the risk, predictability, and consequences of acute pulmonary toxicity from amiodarone in patients undergoing ICD implantation have not been previously described. We reviewed the records of 99 consecutive patients undergoing ICD implantation at our institution from October 1987 to April 1992. Thirty-nine patients were taking 480 +/- 230 mg of amiodarone (median 400 mg, lower 20th percentile 400 mg, upper 80th percentile 800 mg) for 291 +/- 554 days prior to ICD implantation. Ten patients taking amiodarone developed acute pulmonary toxicity clinically manifesting as diffuse pulmonary infiltrates on chest radiography and adult respiratory distress syndrome with hypoxia (arterial pO2 < 60 mmHg) without evidence of pneumonia or elevated pulmonary capillary wedge pressure (PCW < or = 15 mmHg). Of the 60 patients not taking amiodarone none developed adult respiratory distress syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epinephrine-induced lactic acidosis in the setting of status asthmaticus

A relationship between intravenous epinephrine infusion and the development of lactic acidosis has been well described. We report a temporal association between the administration of subcutaneous epinephrine and the development of lactic acidosis in the setting of status asthmaticus. A 20-year-old woman with a history of asthma came to the emergency service in acute respiratory distress and was treated with subcutaneous epinephrine. Six hours later, serial arterial blood gas studies revealed the onset of a primary metabolic acidosis. Additional diagnostic studies revealed a serum lactate level of 9.5 mumol/L. The lactic acidosis resolved within 15 hours. The patient never exhibited signs of hypotension, hypoxemia, or sepsis, and other potential etiologies for lactic acidosis were excluded. We believe the events of this case constitute a new observation and theorize a mechanism of peripheral vasoconstriction and transient tissue hypoperfusion mediated by the subcutaneous epinephrine.     

Angioedema associated with angiotensin II receptor antagonist losartan

Angioedema has not been associated with losartan therapy in hemodialysis patients, as it has been with angiotensin converting enzyme (ACE) inhibitors. We report the case of a hemodialysis patient who previously had angioedema after therapy with ACE inhibitors and again had angioedema while taking losartan. We suggest caution in using losartan in patients with known sensitivity to ACE inhibitors manifested by angioedema.     

First report of association of chronic pancreatitis, primary biliary cirrhosis, and systemic sclerosis

We report an original observation of chronic pancreatitis associated with primary biliary cirrhosis and systemic sclerosis. The diagnosis of each of these conditions was unequivocally confirmed. Pancreatic involvement in this case was asymptomatic. The association of chronic pancreatitis with primary biliary cirrhosis has been previously reported and pancreatitis has been associated with other autoimmune disorders. We hypothesize about the underlying pathogenic mechanisms of chronic pancreatitis in our case.     

Evaluation of the clinical usefulness of APACHE II and SAPS systems in the initial prognostic classification of acute pancreatitis: a multicenter study

The clinical usefulness of the APACHE II and SAPS systems in the early prognostic classification of patients with acute pancreatitis has been evaluated in a prospective multicenter study. We aimed to identify early those patients with acute pancreatitis who should be monitored closely to expedite the detection and treatment of complications. One hundred eighty-two patients with acute pancreatitis were included; 28 were classified as severe, having developed at least one major complication of the disease. The scores obtained through the APACHE II and SAPS systems in these severe cases were significantly higher than the scores in the mild cases of acute pancreatitis (p < 0.001). The sensitivity of these systems in the prognostic classification of acute pancreatitis was 70.4% for APACHE II and 66.7% for SAPS, and the specificity was 79.1% for both. When applying APACHE II and SAPS systems in the early phase of acute pancreatitis, the possibility of misdiagnosing the severity exists, thus limiting the application of these systems in the initial assessment of prognostic classification. In conclusion, APACHE II and SAPS systems are of limited clinical utility in the early prognostic evaluation of acute pancreatitis because of their low positive predictive value.     

Acute pancreatitis secondary to ifosfamide

Acute pancreatitis in cancer patients can be secondary to the malignant process itself. It is also a rare complication of antineoplastic agent administration. Ifosfamide is an effective drug in the treatment of several tumors and has known neurologic, renal, and hematologic toxicities. There is only one recent report in the literature of pancreatitis associated with ifosfamide. We report a case of a 65-year-old woman with small cell bronchogenic carcinoma without pancreatic metastases who developed acute pancreatitis after ifosfamide administration.     

Mortality after vascularized pancreas transplantation

BACKGROUND: Intravenous almitrine, which augments hypoxic pulmonary vasoconstriction, is used for short-term improvement of arterial oxygenation. However, recent research has suggested a potentially harmful effect on lactate metabolism and hepatic function. METHODS: Arterial oxygenation, hemodynamic parameters, plasma lactate, and hepatic function were monitored prospectively in 25 patients with acute lung injury (defined as a ratio of arterial oxygen pressure to inspiratory oxygen fraction < or = 150 mmHg) who where treated with intravenous almitrine. In 21 of 25 patients, acute lung injury was related to primary lung lesions, including pneumonia, postcardiosurgical atelectasis, and lung contusions. RESULTS: Intravenous almitrine increased the ratio of arterial oxygen pressure to inspiratory oxygen fraction from 93 +/- 33 mmHg to 207 +/- 107 mmHg (mean +/- SD). In eight patients (three men), the plasma lactate concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and bicarbonate concentration both decreased during the first 24 h of treatment. In this group of patients, the total bilirubin concentration was elevated before almitrine administration, and the results of other hepatic function tests, such as aspartate aminotransferase, alanine aminotransferase, and prothrombin time, were altered by almitrine administration. Therefore, intravenous almitrine was discontinued. Lactic acidosis and hepatic dysfunction improved. In the other 17 patients (14 men), the plasma lactate concentration and the hepatic function tests remained unaltered during intravenous almitrine therapy for > 60 h. Univariate and multivariate analyses revealed that an abnormal plasma concentration of total bilirubin before almitrine administration and female gender were the two factors significantly linked with lactic acidosis during almitrine infusion. CONCLUSIONS: This study confirms that intravenous almitrine greatly improves arterial oxygenation in patients with acute lung injury but may also induce lactic acidosis and hepatic dysfunction. The coexistence of lactic acidosis and hepatic dysfunction in the same patients strongly suggests that the liver is the primary source of intravenous almitrine-induced lactic acidosis.     

Spontaneous bacterial peritonitis associated with acute viral hepatitis

Spontaneous bacterial peritonitis (SBP) occurs most frequently in patients with cirrhosis and preexistent ascites; SBP has not been previously recognized in association with acute liver disease. We report two patients with acute hepatitis B infection who developed SBP. Patient 1 had Streptococcus pneumoniae peritonitis and bacteremia, but did not have ascites until after the peritoneal infection was evident. Subsequent liver biopsy and follow-up studies confirmed the clinical diagnosis of acute hepatitis. Patient 2 had submassive hepatic necrosis due to hepatitis B and developed ascites before Streptococcus fecalis SBP. Although the association of SBP with acute hepatic injury is rare, these two patients illustrate that the syndrome of SBP does occur with acute liver disease.     

Facial palsy in Kawasaki syndrome

Facial nerve palsy, a very rare complication of Kawasaki syndrome, has been reported in only 25 patients. We treated a 12-week-old boy with bilateral coronary artery aneurysms due to Kawasaki syndrome who developed marked unilateral peripheral facial nerve palsy on day 36 of illness. None of the 25 previously reported patients with this complication were treated with immunoglobulin; they required 7 to 90 days to recover. In our patient, treatment with this agent was associated with complete resolution of facial nerve palsy within 36 hours. Review of prior cases demonstrates that children with Kawasaki-associated facial nerve palsy have more than twice the risk for coronary artery aneurysm (52% vs <25%) as that of children who do not develop this neurological complication. Unexplained facial nerve paralysis in young children with a prolonged febrile illness should provoke consideration of Kawasaki syndrome and of echocardiography to exclude coronary artery aneurysms. Although facial palsy appears likely to resolve in all patients that survive the acute phase of Kawasaki syndrome, treatment with intravenous immunoglobulin appears to considerably shorten the time to full recovery and provides an important clue to the mechanisms of neurological injury in this illness.