Federico Innocente

True versus Mild Hyperthermia during Isolated Hepatic Perfusion: Effects on Melphalan Pharmacokinetics and Liver Function

Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been recently proposed as an alternative therapeutic option for patients with unresectable liver tumors. Although melphalan–heat antiblastic synergism is at a maximum at temperatures higher than 41 °C, IHP has so far been performed in humans at lower temperatures. In this experimental work, we compared IHP under mild versus true hyperthermic conditions in terms of drug pharmacokinetics and liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean temperature of 40 °C (group A, n = 5) or 42 °C (group B, n = 5). After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to-plasma leakage was monitored using scintigraphy. Throughout perfusion, samples from the systemic blood, perfusate, and liver parenchyma were obtained to measure melphalan concentrations. Liver function was assessed using standard blood tests and the indocyanine green-based test. No deaths related to the IHP procedure were recorded. All animals had transient liver function impairment, with all liver function test results returning to normal within the observation period. At histologic examination, liver damage was similar under both hyperthermic conditions. Melphalan levels in the perfusate were not significantly different in the two study groups (the mean perfusate/plasma area under the curve from 0 to 60 minutes ratios were 463 and 501, respectively). These results correlated well with those obtained using the scintigraphic method. Liver drug concentrations remained unchanged after true hyperthermia IHP. Under true hyperthermic conditions, neither an increase in liver parenchyma toxicity nor changes in melphalan pharmacokinetics were observed. These findings support the use of true hyperthermia in the clinical setting to exploit fully the antitumor synergism between melphalan and heat.

Tracheal intubation under fluoroscopic control X ray-guided orotracheal intubation in three cases of impossible direct laryngoscopy

Three patients are described in whom it was impossible to visualise the larynx at direct laryngoscopy. Tracheal intubation was successfully and rapidly achieved with the aid of continuous fluoroscopy.

Recovery profiles of general anesthesia and spinal anesthesia for chemotherapeutic perfusion with circulatory block (stop-flow perfusion)

BACKGROUND:Chemotherapeutic stop-flow perfusion is a new investigational treatment for locally advanced cancers that is usually performed under general anesthesia (GA), and, less frequently, under spinal anesthesia (SA). We designed this clinical trial to compare the clinical profiles of GA and SA for stop-flow perfusion. METHODS:Anesthesia and recovery times, scores on visual analog scales for postoperative pain, and postoperative nausea and vomiting, and admission to the postanesthesia care unit were measured in 40 cancer patients who randomly received either GA with propofol, nitrous oxide/sevoflurane, and fentanyl, or SA with bupivacaine hydrochloride for lower limb or pelvic stop-flow perfusion. RESULTS:GA and SA did not differ in times to achieve home readiness or patient satisfaction. Compared with GA, SA significantly (P < 0.05) reduced anesthesia times (34 vs 16 min), postoperative visual analog scale scores for pain (5 vs 0) and nausea (8 vs 2), and the number of admissions to the postanesthesia care unit (9 vs 0). CONCLUSIONS:For stop-flow perfusion, GA and SA are both effective, but SA provides faster recovery, superior analgesia, and less postoperative nausea and vomiting in the immediate postoperative period.

Low-dose ketamine with clonidine and midazolam for adult day care surgery.

EDITOR: The ideal anaesthetic for day-surgery procedures should give quick recovery without pain, nausea or vomiting and ensure a rapid return to preoperative mental state with rapid discharge and patient satisfaction. Ketamine was introduced into clinical practice nearly 40 yr ago but its use has declined. It nevertheless remains in regular use in certain surgical disciplines, e.g. paediatrics, plastic and burn surgery, during emergencies or during short diagnostic procedures. However, when administered to adult patients as the sole anaesthetic it frequently causes emergence reactions characterized by anxiety and hallucinations. A number of agents, including midazolam and clonidine, have been used to reduce or prevent these reactions. The aim of the present study was to test whether the combination of low-dose ketamine with midazolam, clonidine and ketorolac but without opioid administration, could provide adequate anaesthesia for interventions with low-to-medium pain potential performed on a day-surgery basis. This included breast surgery, laparoscopy, superficial excision of minor lesions, thoracoscopy, appendicectomy and proctological surgery. Five hundred patients, (172 males and 328 females) ASA Grade I–II, were enrolled in the study. All gave written, informed consent and were instructed in the use of the visual analogue scale (VAS). Overall mean age was 53.9 (SD 12.2) yr and mean weight 76.1 (SD 22.5) kg. Sedation was assessed using the Observer’s Assessment of Alertness/Sedation Scale (OAA/S) [1] and cognitive function was assessed with the Mini Mental State Examination [2]. The Profile of Mood State was used to assess mood [3]. Heart rate (HR), respiratory rate, oxygen saturation and arterial pressure were measured before and during surgery and for 1 h afterwards. Before induction of anaesthesia with propofol 2 mg kg 1, patients were given atropine 0.01 mg kg 1, midazolam 0.03– 0.05 mg kg 1 and ketamine 0.4 mg kg 1 all intravenously (i.v.). All patients received nitrous oxide 65% in oxygen. Muscle relaxation was obtained with suxamethonium (1.0–1.5 mg kg 1) or vecuronium (0.1 mg kg 1) for tracheal intubation and maintained with vecuronium. After tracheal intubation patients were given clonidine 150 μg i.v. If depth of anaesthesia was not adequate (blood pressure, BP or HR 20% of the preinduction values, lacrimation and sweating) patients were given ketamine 0.4– 0.6 mg kg 1 (maximum total dose 1 mg kg 1) or bolus injections of propofol 0.5 mg kg 1. The last ketamine administration was at least 1 h before the end of surgery. Ketorolac 30 mg and dexamethasone 8 mg were administered i.v. 30 min before wound closure. Total dose of ketamine used was 0.6 (SD 0.2) mg kg 1. At the end of the procedure, neuromuscular block was reversed using neostigmine, nitrous oxide was discontinued and the interval from this time to eye opening was recorded. Overall mean duration of surgery and anaesthesia were 121.4 (SD 60.1) min and 146.4 (SD 63.5) min, respectively. Time from discontinuation of nitrous oxide to eye opening was 176.9 (SD 106.1) s. Immediately after extubation and every 10 min thereafter, VAS scores for pain, sleepiness and nausea, OAA/S, and Aldrete score [4] were measured. In the first postoperative hour, ketorolac 0.3–0.6 mg kg 1 was administered if VAS for pain was 30. Patients were discharged from the recovery room when two consecutive Aldrete scores were 9 and all VAS scores were 30. At this time, the Profile of Mood State and Mini Mental State examination were repeated and patients were asked whether they felt strange or disoriented. Vital signs, nausea, pain, sleepiness and readiness for discharge from the hospital were assessed at 2, 3 and 4 h from the end of surgery. Patients were judged ‘ready for discharge’ (even if not actually dismissed from the hospital) when they had stable vital signs: no nausea, were oriented, able to ambulate unassisted Correspondence to: Carlo Ori, Dipartimento di Farmacologia ed Anestesiologia, Sezione di Anestesiologia e Rianimazione, Università degli Studi di Padova, via C. Battisti, 267 35121 Padova, Italy. E-mail: carloori@unipd.it; Tel: 39 0498213090; Fax: 39 0498754256