High-dose intravenous metoclopramide and intermittent intramuscular prochlorperazine and diazepam in the management of emesis induced by cis-dichlorodiammineplatinum.

Intravenous metoclopramide and IM prochlorperazine and diazepam were compared in the management of vomiting occurring during treatment with cis-dichlorodiammineplatinum (cis-platinum). A total of 104 cycles in 30 patients were evaluated. Twenty-two patients took part in a cross-over study in which emetic profiles for each patient managed with each anti-emetic schedule were compared. In all, 44 cycles of treatment in 22 patients were evaluated as part of a cross-over study. No significant difference in emetic control was observed between the two anti-emetic regimens. The side-effects observed using IV metoclopramide included extrapyramidal phenomena (19%) and flushing attacks (16%).

Intraperitoneal 5-fluoro-2'-deoxyuridine (FUDR) and (S)-leucovorin for disease predominantly confined to the peritoneal cavity: a pharmacokinetic and toxicity study.

Intraperitoneal (IP) administration of fluorinated pyrimidines has been evaluated for ovarian and gastrointestinal malignancies in phase I, II, and III trials. The tolerance and pharmacokinetic profile of IP 5-fluoro-2'-deoxyuridine(FUDR) alone and with (R,S)-leucovorin ((R,S)-LV) have each been evaluated in previous phase I studies. FUDR doses of 3 g per day with and without (R,S)-LV doses up to 640 mg per day given IP are well tolerated. The current phase I study was designed to determine the pharmacokinetic profiles and clinical tolerance of escalating doses of the pure biologically active S-isomer of leucovorin ((S)-LV) given IP with the same dosing schedule of FUDR. A group of 16 patients with disease confined to the abdominal cavity were treated in this study. Pharmacokinetic studies of blood and peritoneal fluid, toxicity profiles, and clinical response for the first three cycles are reported here. The toxicity profile did not significantly differ from the prior two studies. All non-hematologic toxicities, such as fatigue, nausea, vomiting, diarrhea, and abdominal discomfort were less than grade 4, and most were less than grade 3. Neutropenia and thrombocytopenia were uncommon and observed only in patients with compromised bone marrow reserve. The pharmacokinetic profiles were also congruent with the previous studies and indicate a three-log advantage for FUDR. The (S)-LV profiles in the peritoneal cavity paralleled those of FUDR. Antitumor effects or absence of progression until after cessation of therapy were documented in 11 patients. At a median follow-up of 18 months 44% of patients were alive. IP administration of 3-g of FUDR and up to 640 mg (S)-LV daily for three days was well tolerated. The tolerance and antitumor effects observed during IP FUDR and LV in these studies encourage further exploration of this regimen against ovarian and gastrointestinal malignancies. The actual role and optimal dose of LV as an enhancer of the antitumor actions of FUDR administered by this route remain unknown.

Modification of tonic-clonic convulsions by atracurium in multiple-monitored electroconvulsive therapy.

STUDY OBJECTIVE: To determine the effect of two different doses of atracurium on the modification of tonic-clonic convulsions in multiple-monitored electroconvulsive therapy (MMECT). To compare recovery time and adverse reactions of these doses. DESIGN: Clinical study. Anesthesiologist was blinded in the evaluation of post-electroconvulsive therapy (ECT) myalgia and other side effects. SETTING: University-affiliated veterans general hospital. PATIENTS: Two groups of twelve psychiatric inpatients who suffered from major depression or catatonic-type schizophrenia that failed to respond to tricyclic antidepressant therapy. INTERVENTIONS: Under single-channel, prefrontal electroencephalographic (EEG) monitoring, patients were given either 0.3 mg/kg or 0.5 mg/kg of atracurium intravenously (IV) after anesthetic induction with methohexital 1 mg/kg i.v. MEASUREMENTS AND MAIN RESULTS: Evoked electromyographic responses of the adductor pollicis muscle was obtained by train-of-four stimulation of the ulnar nerve at the wrist every 20 seconds. The first twitch depression (T1) of neuromuscular blockade was maintained within 11% to 25% (atracurium 0.3 mg/kg) or 0% to 10% (atracurium 0.5 mg/kg) of control during the entire session of MMECT. Patients pretreated with atracurium 0.5 mg/kg had significantly fewer ECT-induced moderate and vigorous convulsions when compared with patients receiving atracurium 0.3 mg/kg (16.7% vs. 78.4%, moderate; 0% vs. 8.3%, vigorous). However, patients pretreated with atracurium 0.5 mg/kg took a longer time to attain a T4 ratio of 0.5 than did patients receiving atracurium 0.3 mg/kg (9.2 +/- 0.8 minutes vs. 4.3 +/- 0.4 minutes). There was no significant difference between the two groups with respect to cumulative seizure duration or frequency of bradycardia, sialorrhea, postseizure myalgia, nausea, headache, or confusion. No patient in either group recalled any event concerning electroconvulsive shock. CONCLUSIONS: Whereas full neuromuscular blockade by atracurium 0.5 mg/kg i.v. is very effective in the modification of tonic-clonic convulsions induced by ECT, we suggest that a lower dose of atracurium (0.3 mg/kg i.v.) be used if one needs to ascertain the occurrence of ECT-induced seizures as indicated by minimum peripheral muscle activity at the time of EEG recording during MMECT.

Multidisciplinary team working: is it both holistic and effective?

Multidisciplinary team (MDT) working has been endorsed as the main mechanism to ensure truly holistic care for patients and a seamless service for patients throughout their disease trajectory and across the boundaries of primary, secondary, and tertiary care. However the effectiveness of each team needs to be continually evaluated to ensure that all the relevant disciplines are able to participate in the clinical management of patients. This article describes the work of the Cancer Services Collaborative at the Birmingham Women's hospital in the UK in promoting the development of a holistic MDT in parallel with the medical model.