Oppenheim C, Stanescu R, Dormont D, et al. False-negative diffusion- weighted MR findings in acute ischemic stroke. AJNR Am J Neuro- radiol 2000;21:1434 - 40.

Gonzalez RG, Schaefer PW, Buonanno FS, et al. Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset. Radiology 1999:210;155-62.

Tong DC, Yenari MA, Albers GW, et al. Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (b6.5 hour) ischemic stroke. Neurology 1998;50:864 - 70.

Hemodialysis and hemoperfusion in a patient with an isolated phenytoin overdose^B

Phenytoin is a commonly used anticonvulsant medica- tion frequently associated with overdose and suprathera- peutic levels resulting in ataxia and nystagmus. Reports of serious morbidity or mortality are rare, and treatment usually consists of observation and Safety precautions. At therapeutic serum concentrations, hepatic metabolism is first order, with drug metabolism increasing as the drug concentration increases [1]. At supratherapeutic levels such as in the case of intentional drug overdose, hydroxylation of the parent drug in the liver is saturated and phenytoin metabolism occurs as a zero-order process (the amount of drug metabolized per a given period is constant), thereby undergoing a significantly prolonged elimination half-life increasing from 25 hours at therapeutic concentrations of 15 mg/L to more than 60 hours when levels exceed 40 mg/L [2]. Various methods to improve drug elimination in the rare case of severe overdose have been entertained. Because phenytoin has a small volume of distribution (V_d = 0.7 L/kg), is well adsorbed to activated charcoal, and may exceed total protein-binding capabilities of albumin in overdose, hemodialysis (HD) and charcoal hemoperfusion (HP), or even the use of the molecular adsorbent recirculating system, a blood-purification system based on albumin dialysis that includes a charcoal filter, offer some theoretical utility [3]. However, because of the size and high protein binding of phenytoin, it has been argued that these methods are unlikely to be helpful. We report on a case of Phenytoin toxicity with extremely high levels treated with HD and HP without evidence of improved clinical outcome.

A 32-year-old man arrived in the ED 1 hour after ingesting approximately 175 tablets of 100-mg phenytoin tablets. He was given 50 g of oral activated charcoal en route. He arrived at the ED with ataxia and nystagmus. His vital signs were as follows: blood pressure, 130/72; heart rate, 92; respiratory rate, 18; temperature, 37.48C. He was awake and alert and oriented with an initial 2-hour level of

41.2 mg/L. He was treated with an additional 25 g of activated charcoal and was admitted to the medicine ward. The repeat phenytoin level 6 hours later was 96 mg/L. Owing to his mental status, obtundation, and emesis leading

to possible aspiration, the patient was intubated and transferred to the intensive care unit. During the following days, the patient remained intubated and obtunded with a phenytoin level of 91 mg/L on hospital day 4. On hospital day 8, HP was planned as the patient was still intubated and obtunded with a level of 76 mg/L. Hemodialysis was performed owing to nonavailability of HP cartridges. Four hours after a 4-hour HD session, the phenytoin level was

51.7 mg/L. On day 10, the patient underwent HP as a result of persistent mental status alterations, ileus, and Aspiration pneumonia. Before a 4-hour HP session, his phenytoin level was 53 mg/L, and it fell to 38 mg/L 4 hours after the session (see Table 1). The level rebounded to 52 mg/L the next day. During the subsequent 2 weeks, the patient’s level fell and the patient was extubated. The patient has had 1 year of subsequent cognitive and functional impairment that has slowly improved with rehabilitation.

Hemodialysis is likely to be useful in small compounds that are water soluble, not protein bound, or that have weak binding constants to plasma proteins. Multiple-dose acti- vated charcoal and charcoal HP may be useful if a drug has low endogenous clearance, is weakly or incompletely protein bound, has a relatively small V_d, and is well bound to activated charcoal. Theoretically severe overdoses with protein-bound substances may saturate protein-binding sites and allow a better free drug-to-V_d ratio, making the drug more amenable to either HD or HP. Hemodialysis is more readily available and was used first in this case for that reason. Although it appears that HD did lower the Serum phenytoin concentration in this patient, there was no clinical change in the patient’s status. The use of HP did also appear to acutely lower the phenytoin concentration, although the level rebounded quickly and was unchanged the next day. It appears from this isolated case that HD may represent a method to remove phenytoin or substances with similar toxicokinetic properties when a patient is severely affected by such an overdose. However, use of HD, HP, or both must be tempered by comparing the known risks of these interventions, the complications of prolonged intuba-

Table 1 Hospital course

Time Phenytoin

(h) level (mg/L)

2 41.2

96

Relation of level

to intervention

1 h after 50 g of activated charcoal PO 6 h after 25 g of activated charcoal PO

Clinical status

Ataxia,

nystagmus

10

Progressive

obtundation

100 91 Intubated, obtunded

tion and intensive care treatment, and the unproven clinical efficacy of HD and HP in such settings.

We reported on a case of an isolated severe phenytoin overdose with long-term adverse sequelae and the use of HD and HP on a single patient without any apparent clinical improvement and only slight effects on drug serum levels.

Michael A. Miller MD Department of Emergency Medicine Darnall Army Community Hospital Fort Hood, TX 76544, USA

Central Texas Poison Control Center

Temple, TX 76508, USA

Chad S. Crystal MD Department of Emergency Medicine Darnall Army Community Hospital Fort Hood, TX 76544, USA

Manish M. Patel MD Department of Emergency Medicine Emory University, Atlanta, GA, USA

doi:10.1016/j.ajem.2006.02.011

References

1. Rall T, Schlerfer L. Drugs effective in the therapy of the epilepsies. In: Gilman A, Goodman L, Rall T, et al, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. New York7 MacMillan; 1990.

   p. 436 - 44.

   Tozer T, Winter M. Phenytoin. In: Evans W, Schentag J, Jusko W, editors. Applied pharmacokinetics. Spokane7 Appl Ther; 1980. p. 275 - 314.

2. Sen S, Ratnaraj N, Davies NA, Mookerjee RP, Cooper CE, Patsalos PN, et al. Treatment of phenytoin toxicity by the molecular adsorbents recirculating system (MARS). Epilepsia 2003;44(2):265 - 7.

   A case report of Emphysematous pyelonephritis secondary to ureteral obstruction in a non-Diabetic patient

   A 74-year-old woman was brought to the emergency department after being found by her niece on the floor of her apartment, confused and incontinent of urine and stool. According to her niece, the patient had been complaining of flank pain for several days. The patient’s medical history included hypertension; gastric cancer status post resection, radiation, and chemotherapy 3 years prior; and pulmonary embolus. She did not have a history of diabetes mellitus.

   Initial vital signs showed a temperature of 97.38F, heart rate of 72 beats per minute, blood pressure of 91/41 mm Hg, and a respiratory rate of 16 breaths per minute. Physical examination was remarkable only for a pale, thin Elderly woman who appeared uncomfortable and was slightly disoriented.

   Because of persistent hypotension, dopamine and lev- ophed drips were started. A Foley catheter was placed with

   

   Fig. 1 non-contrast CT scan of abdomen.

   return of no urine. Standard laboratory tests revealed a white blood cell count of 19300/mm³, lactate of 4.1 mg/dL, blood urea nitrogen of 54 mg/dL, and creatinine of 4.0 mg/dL. The patient had a non-contrast CT scan of the abdomen and pelvis to rule out ruptured Abdominal aortic aneurysm. The CT scan revealed a right Ureteral stone with significant right hydronephrosis and surrounding mesenteric stranding and gas within the renal collecting system (Figs. 1 and 2).

   The patient was diagnosed with urosepsis, acute renal failure, and emphysematous pyelonephritis secondary to an obstructing ureteral stone. The urologic service and vascular interventional radiology service were consulted immediately, and the patient was sent to the vascular interventional radiology suite for an emergent percutaneous nephrostomy tube. The patient briefly stabilized, however, then deterio- rated several days later, suffered a cardiac arrest, and died after unsuccessful attempts at resuscitation.

   Emphysematous pyelonephritis is a rare and potentially fatal form of complicated, necrotizing pyelonephritis. Almost 90% of cases are found in diabetic patients with poor Glycemic control [1,2]. Emphysematous pyelonephritis can also be caused by urinary tract obstruction due to calculi, neoplasm, or stricture [3].

   Emphysematous pyelonephritis is diagnosed when gas is seen within the renal parenchyma or within the perinephric tissue. Plain abdominal radiography has very limited ability to demonstrate gas [4]. ultrasound evaluation of gas within the kidney will show echogenic areas within the renal parenchyma and surrounding tissues with irregular shadow- ing posterior to the echogenic areas. However, large amounts of gas may obscure the entire kidney, or the presence of gas may be difficult to assess when a large amount of fluid is also present [5]. The diagnostic method of choice is the non-contrast CT scan. In addition to showing the presence of gas, a CT scan can be used to assess the extent of involvement within the kidney and can diagnose obstruction [5,6].