Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact. AIM: To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off. PATIENTS AND METHODS: Patients (n = 139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations. RESULTS: All the patients with a PCI ≥ 15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was <15 vs 12% when it was ≥ 15 (p < 0.0001. The multivariate analysis retained two prognostic factors: PCI ≥ 15 (p = 0.02, HR = 1.8), and the involvement of area 12 (lower ileum) (p = 0.001, HR = 3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI <15 and area 12 involved was 15%, close to that of patients with a PCI ≥ 15 (12%) and far lower than that of patients with a PCI <15 and no area 12 involvement (70%). CONCLUSION: A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS + HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.

Major abdominal surgery for cancer: does epidural analgesia have a long-term effect on recurrence-free and overall survival?

BACKGROUND: Retrospective studies have suggested that regional analgesia combined with general anaesthesia could decrease cancer recurrence. The purpose of this study was to assess the influence of regional analgesia on recurrence-free (RFS) and overall survival in patients undergoing major intra-abdominal surgery for cancer. METHOD: Patients previously included in a prospective randomized study comparing two postoperative techniques of analgesia were retrospectively studied. The EP group received general anaesthesia with bupivacaine thoracic epidural analgesia and the SC group received general anaesthesia with fentanyl followed by continuous subcutaneous morphine. RESULTS: One hundred and thirty-two patients were analyzed (63 and 69 in SC and EP group, respectively) with a 17-year-median follow-up. After 5 years, RFS was 43% [95% CI: 32%-55%] in EP group and 24% [95% CI: 15%-36%] in SC group, but the difference did not reach statistical significance for RFS nor for overall survival (P=0.10 and 0.16 respectively). Using multivariable analysis over the whole follow-up period, the type of analgesia was not a statistically significant predictive factor for RFS (EP/SC, HR=1.3 [95% CI: 0.8-2.0%]). The anaesthesia effect changed moderately over the follow-up and HR for overall survival (EP/SC) reached statistical significance after 5, 6 and 8 years. CONCLUSION: Despite a trend in favour of the epidural, this retrospective review of patients included in a previous randomized study failed to demonstrate a statistically significant association between the perioperative analgesia and RFS after abdominal surgery for cancer. The duration of follow-up may have an impact on the analgesia effect on survival.

Assessing the clinical or pharmaco-economical benefit of target controlled desflurane delivery in surgical patients using the Zeus anaesthesia machine.

The Zeus anaesthesia machine includes an auto-control mode which allows targeting of end-tidal volatile and inspired oxygen concentrations. We assessed the clinical benefits and economic impact of this target-controlled anaesthesia compared with conventional manually controlled anaesthesia. Eighty patients were randomly assigned to receive desflurane either with a fresh gas flow set by the anaesthetist or in auto-control mode. Drug delivery was adjusted to maintain bispectral index between 40-60 units and systolic arterial pressure under 15 mmHg above its pre-induction value (upper limit) and over 90 mmHg (lower limit). Blood pressure was maintained in the desired range for 89% and 91% of the maintenance period for auto-control and manual control respectively (p = 0.49). Bispectral index was in the desired range for 82% and 79% of the maintenance period, for auto-control and manual control respectively (p = 0.46). Oxygen consumption was more than halved by the use of auto-control mode, and mean (SD) desflurane consumption during surgery was 0.07 (0.04) vs 0.2 (0.07) ml.min(-1) in auto-control and manual control respectively (p < 0.0001). The number of drug delivery adjustments per hour was significantly lower in auto-control mode (mean (SD) 7 (2) vs 15 (12); p < 0.0001). Thus, the auto-control mode provided similar haemodynamic stability and bispectral control as did conventional manually controlled anaesthesia, but led to a reduction in gas and vapour consumption with a more clinically acceptable workload.

[Anaesthesia for endocrine tumor removal]. / Anesthésie pour traitement des tumeurs endocrines.

Endocrine tumors could be defined by their ability to produce structural proteins or hormones common to nervous and endocrine cells. They might induce physiological transforms or outcome adverse events which should be well known in order to prevent or treat them early. The goal of this review was to describe these changes, to describe preoperative assessment, and to discuss intraoperative monitoring and drugs choice based on the literature from the last 30 years. As an example, it should be noticed that: (1) preoperative blood pressure control is essential to prepare phaeochromocytoma for surgery. It should be followed during anaesthesia by intensive fluid load, reversible anaesthetic drugs and rational cardiovascular medications use (as for example remifentanil, sevoflurane, calcium channel blockers and esmolol), and after surgery by narrow clinical and biological monitoring; (2) after medullar thyroid cancer, main adverse events include cervical compressive haematoma and recurrent laryngeal nerve injury as for any thyroid surgery; (3) during pituitary surgery, air embolism might be expected, whereas water dysregulation (diabetes insipidus), corticotroph insufficiency, cerebrospinal fluid (CSF) leak might occur postoperatively. In acromegaly, difficult endotracheal intubation is possible whereas severe Cushing's syndrome may be complicated with hypertensive cardiac failure, infections, thrombosis, delayed cicatrisation; (4) somatostatine analogs are a keystone in carcinoid tumors preoperative and anaesthetic management.

[Which settings to optimize anaesthetics delivery: fresh gas flow or delivered fraction?]. / Optimisation de l'administration des agents anesthésiques inhalés : débit de gaz frais ou fraction délivrée ?

INTRODUCTION: During volatile closed-circuit anaesthesia, a chosen end-tidal fraction (Fet) could be achieved by setting either delivered fraction (Fd) or fresh gas flow (FGF). This study compared the efficacy of both strategies and the resulting drug consumption. PATIENTS AND METHODS: Sixty patients (10 per group) were administered, after intravenous induction and intubation, desflurane, sevoflurane or isoflurane+50% N(2)O, to achieve a target Fet equal to one minimal alveolar concentration (MAC), according to one strategy: high FGF (HFGF) Fd fixed 20% above target Fet, FGF 10 l/min then 1l/min after achieving the target, FGF opened at 10 l/min at the end of surgery; low FGF (LFGF) FGF fixed at 1l/min, Fd at the maximal value on the vaporizer, then set at target Fet+20% after achieving Fet equal to one MAC, FGF maintained at 1l/min until extubation. RESULTS: The target Fet was achieved in all patients in LFGF within 2.1+/-0.9 min followed by 15% (isoflurane) to 57% (sevoflurane) overdosage, but only in nine patients out of 30 after 10 min in HFGF. Delays were similar between desflurane and sevoflurane. Volatile consumption was decreased by 75% in LFGF. Fifty percent decrement and extubation times were shorter with HFGF, similarly for the three agents. CONCLUSION: Massive overdosage of Fd is the fastest, reproducible and cheapest strategy to achieve (or to increase) a chosen Fet. High FGF is the fastest to decrease Fet during or at the end of anaesthesia. Combining Fd and FGF adjustments in order to maximize Fd/Fet gradients overwrites pharmacokinetic differences between desflurane and sevoflurane and reduces differences with isoflurane. Automatic adjustments based on volatile pharmacockinetics would be helpful to achieve a target Fet without overdosage.

[Falsely elevated-bispectral index]. / Un indice bispectral étrangement élevé

We report a case of a falsely elevated-bispectral index (BIS) during a general anaesthesia combining remifentanil TCI, desflurane and nitrous oxide for an isolated-limb chemotherapy. During surgery, BIS increased and stabilized around 70, with neither residual neuromuscular blockade nor clinical sign of awareness. These high BIS values were attributed to high-electromyographic activity and electric artefacts, such as extracorporeal-circulation machine and tourniquet. At the end of the surgery, the BIS returned to expected values around 50. The patient did not complain of intraoperative recall. This case reminds us that the BIS has some limits as being sensitive to EMG or environment artefacts that should be eliminated before deepening anesthesia. To do so, a decision algorithm is proposed that may be used for all situations of surprising high BIS, taking into account the level of neuromuscular blockade, clinical response to orders and the presence of devices likely to induce electrical or mechanical artefacts.

Peritoneal pseudomyxoma: results of a systematic policy of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Pseudomyxoma peritonei (PMP) is characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured, possibly malignant mucinous neoplasm of the appendix. Treatment based on complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is gaining support. The aim of this study was to identify pre- and perioperative factors of prognostic value. METHODS: A total of 105 patients (with no residual tumours exceeding 2 mm) were treated with CCRS plus HIPEC based on oxaliplatin. Clinical, radiological, pathological factors and blood markers were analysed to determine their prognostic value for survival. RESULTS: Mortality (7.6 per cent) and morbidity (67.6 per cent) were significantly correlated with peritoneal index, pathological grade and blood CA19.9 level. The median follow-up was 48 months. Seven patients died after hospital discharge. Overall and disease-free 5-year survival rates were 80.0 and 68.5 per cent respectively. The Cox model identified only two significant factors impacting on disease-free survival: CA19.9 level and pathological grade. CONCLUSION: CCRS is the most effective treatment for PMP, and adding HIPEC prolongs long-term survival. Further strategies should focus on improving postoperative outcome in extended PMP.

Remifentanil and other opioids.

Most opioids used in anaesthesia are of the anilidopiperidine family, including fentanyl, alfentanil, sufentanil and remifentanil. While all share similar pharmacological properties, remifentanil, the newest one, is probably the most original, which is the reason this review focusses especially on this drug. Remifentanil is a potent mu-agonist that retains all the pharmacodynamic characteristics of its class (regarding analgesia, respiratory depression, muscle rigidity, nausea and vomiting, pruritus, etc.) but with a unique pharmacokinetic profile that combines a short onset and the fastest offset, independent of the infusion duration. Consequently, it offers a unique titratability when its effects need to be quickly achieved or suppressed, but it requires specific drug delivery schemes such as continuous infusion, target-controlled infusion and anticipated postoperative pain treatment. Kinetic differences between opioids used in anaesthesia and some clinical uses of remifentanil are reviewed in this chapter.

Pressure support ventilation during fibreoptic intubation under propofol anaesthesia.

GOAL OF THE STUDY: To assess the benefit of pressure support ventilation during fibreoptic intubation performed under propofol anaesthesia in patients having an anticipated difficult intubation. PROCEDURES: Thirty-two patients with ENT cancer, and having at least two criteria for anticipated difficult intubation were prospectively included. All patients received topical lidocaine 2% and propofol by plasma target control infusion (initial target concentration 3 microg ml(-1), then adjusted to maintain loss of consciousness without apnoea). They were randomly assigned between two groups: spontaneous breathing (SB) or pressure support ventilation (with a support level set at 10 cm H(2)O) both using Fi(o(2))=1. Conditions for fibreoptic intubation, respiratory parameters (pulse oxymetry, ventilatory frequency, tidal volume and PetCO2 after intubation) and haemodynamic parameters were recorded. RESULTS: Patient characteristic data and intubation conditions were similar between both groups. All patients had a successful fibreoptic intubation and none needed a rescue procedure because of desaturation. In spite of a longer duration of intubation, PE'CO2 after intubation was lower and tidal volume during intubation was higher with pressure support ventilation than in SB patients [38.1 (4.2) vs 42.3 (4.7) mm Hg and 371 (139) vs 165 (98) ml, respectively]. Desaturation episodes were observed in two SB patients conversely to no episode during pressure support ventilation, probably because of the higher minute ventilation. CONCLUSION: Pressure support represents a useful method to improve ventilation during fibreoptic intubation under propofol anaesthesia in patients with an anticipated difficult intubation.

Fibre-optic intubation teaching in sedated patients with anticipated difficult intubation.

BACKGROUND AND OBJECTIVES: The objective of the study was to assess the safety of training fibre-optic intubation performed under propofol light general anaesthesia in patients with an anticipated difficult intubation. METHODS: Patients with ear, nose and throat cancer having at least two criteria for anticipated difficult intubation and scheduled for fibre-optic intubation were included prospectively. In 26 patients, intubation was performed by an anaesthesia resident (under senior supervision), whereas in 20 patients, it was performed by a senior anaesthesiologist. All patients received propofol light general anaesthesia adjusted to maintain both loss of consciousness and spontaneous ventilation. RESULTS: Of the 46 patients, 45 had successful fibre-optic intubation, and one needed a rescue procedure because of hypoxaemia. Residents failed to intubate four patients, who were easily intubated by the senior. Episodic hypoxaemia (SPO2 < 90%) occurred in three patients in each group. No statistically significant difference was found between junior and senior neither on the duration of the procedure (9.3 +/- 4.9 vs. 7.5 +/- 4.0 min) nor on the propofol consumption (197 +/- 130 vs. 193 +/- 103 mg) or the ETCO2 at the end of the procedure (36 +/- 6 vs. 38 +/- 6 mmHg), respectively. CONCLUSION: Teaching fibre-optic tracheal intubation in patients with anticipated difficult intubation and sedated with propofol did not increase morbidity significantly compared with an experienced anaesthesiologist. Fibre-optic intubation under propofol light general anaesthesia could be safely performed by a resident as long as a senior anaesthesiologist is permanently present, spontaneous ventilation is maintained and a rescue oxygenation technique is immediately available.

Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance.

BACKGROUND: The purpose of this study was to report the pharmacokinetics (PK) and tolerance profile of intraoperative intraperitoneal chemo-hyperthermia (IPCH) with oxaliplatin and irinotecan. PATIENTS AND METHODS: Thirty-nine patients with peritoneal carcinomatosis (PC) of either gastrointestinal or peritoneal origin underwent complete cytoreductive surgery followed by IPCH with a stable dose of oxaliplatin (460 mg/m(2)), plus one among seven escalating doses of irinotecan (from 300 to 700 mg/m(2)). IPCH was carried out with the abdomen open, for 30 min at 43 degrees C, with 2 l/m(2) of a 5% dextrose instillation in a closed continuous circuit. Patients received intravenous leucovorin (20 mg/m(2)) and 5-fluorouracil (400 mg/m(2)) just before IPCH to maximize the effect of oxaliplatin and irinotecan. RESULTS: Irinotecan concentration in tumoral tissue increased until 400 mg/m(2) and then remained stable despite dose escalations. It was 16-23 times higher than in non-bathed tissues. Increasing doses of intraperitoneal irinotecan did not modify the PK of intraperitoneal oxaliplatin, and the drug concentration ratio was 17.8 higher in tumoral tissue (bathed) than in non-bathed tissues. The hospital mortality rate was 2.5% and the non-hematological complication rate was 25%. However, grade 3-4 hematological toxicity rate was 58%. CONCLUSION: Intraperitoneal heated oxaliplatin (460 mg/m(2)) plus irinotecan (400 mg/m(2)) presented an advantageous PK profile and was tolerated by patients, despite a high hematological toxicity rate.

Desflurane-remifentanil-nitrous oxide anaesthesia for abdominal surgery: optimal concentrations and recovery features.

BACKGROUND: Intraoperative combinations of volatile and opioid agents are used to achieve unconsciousness, hypnotic sparing, haemodynamic stability and uneventful recovery. This study describes the influence of different remifentanil concentrations on these variables when combined with desflurane during abdominal surgery. METHODS: Sixty-one healthy adult patients were randomly allocated to one of five predefined remifentanil target concentrations (3, 5, 7, 10 or 15 ng ml(-1)). Anaesthesia was titrated to maintain mean blood pressure (MBP), heart rate (HR) and BIS trade mark within predetermined values by adjusting desflurane delivery. Postoperative analgesia using propacetamol and morphine was initiated 30-45 min before skin closure, and continued using morphine PCA. RESULTS: Desflurane requirements adjusted to both BIS and haemodynamics were not significantly modified by the remifentanil concentration (median Fet(DES) 2.7% before incision, 2.5% intraoperatively, and 2.2% during closure), resulting in a calculated drug consumption of 0.22-0.25 ml min(-1) (with 1.5 l min(-1) fresh gas flow). High remifentanil concentration decreased MBP and HR, and reduced the duration of tachycardia, but increased the duration of hypotension. The optimal balance was obtained with a remifentanil concentration of 5-7 ng ml(-1) for intubation, 3 ng ml(-1) until incision, 10 ng ml(-1) during intra-abdominal surgery and 5-7 ng ml(-1) during closure. Post-operative morphine requirements were not significantly modified by intraoperative remifentanil concentrations (median 30 mg/24 h, range [2-88]). CONCLUSION: Remifentanil target concentrations from 3 to 15 ng ml(-1) had little influence on desflurane requirements or postoperative morphine consumption, but markedly modified intraoperative haemodynamic stability, suggesting that the target concentration should closely follow the successive noxious stimulations.

[Survey and budgetary impact of anaesthesia machines failures]. / Surveillance et impact budgétaire des pannes des appareils d'anesthésie.

OBJECTIVE: To assess the incidence and the causes of failures of anaesthesia machines in relation to aging. Study design. - Prospective survey from january 1996 to july 2000. MATERIAL AND METHODS: The causes (mechanical or electronic), the moment of identification (checklist, maintenance operation or quality-control operation) of each anaesthetic machine failure, the repair cost and the maintenance cost of 14 anaesthetic machines have been collected and entered into a database. RESULTS: Over 31,948 anaesthesia delivered during the period of the study, 614 failures have been declared: 53% were related both to mechanical problems or monitoring failure and 40% were identified during the pre-operative checklist. In half of the cases, a specially trained anaesthetic nurse was able to correct the failure in the operating theatre. The annual rate of anaesthetic machine failure remained stable over the study period and the annual maintenance cost is approximatively 10% of the initial machine value. No procedure was cancelled because of a machine technical failure. CONCLUSION: Anaesthetic machine failure rate change according to the time should not be criteria for remplacement if rigorous quality control and maintenance operation are used.

Electrochemotherapy: a new treatment of solid tumors.

Electrochemotherapy is a new local treatment of the solid tumors that can be defined as the local potentiation, by means of permeabilizing electric pulses, of the antitumor activity of non-permeant (e.g. bleomycin) or low-permeant (e.g. cisplatin) anticancer drugs. The electric pulses are delivered locally on the solid tumors, after the intravenous or intralesional injection of the chemotherapy agent. In this review, the basis of the electrochemotherapy are recalled. Then, after summarizing clinical data, we present some results of the European project Cliniporator, as well as the new pulse generator, the Cliniporator, that incorporates new features resulting from this research project, and that is fully conceived for a clinical use. Finally, future perspectives are discussed.

[Target controlled infusion (TCI) anesthesia using propofol. Assessment of training and practice in the operating room]. / Anesthésie intraveineuse à objectif de concentration (Aivoc) avec le propofol. Evaluation des formations et pratiques au bloc opératoire.

OBJECTIVE: To evaluate overall awareness of TCI and the need for training in the TCI technique. To assess, among trained anaesthetists, the value of the session and the impact of TCI technique on their working practice. STUDY DESIGN: Two prospective domestic surveys during the first quarter of 1999. METHODS: Three hundred anaesthetists representative of French anaesthetists as a whole, and 336 anaesthetists who had taken part in a training course. RESULTS: The notoriety of TCI was high and greater in the public sector compared with the private sector. Almost 3/4 of anaesthetists believed that training was necessary but only four anaesthetists out of ten TCI users said they had taken part in training sessions. After the training session nine anaesthetists out of ten became TCI users and would have recommended the training course despite the low number and variety of anaesthetic procedures observed during the practical part of training. The main difficulties reported during initial use were the choice of target concentrations and the management of drug interactions. Familiarisation to the technique was rapid (less than 20 procedures). Despite the lack of long experience (< 6 months for more than 2/3 of them), TCI appeared to be more likely used for anaesthesia of average duration. CONCLUSIONS: TCI was perceived to be an innovative concept with a requirement of a specific training. This preliminary appraisal of training sessions was generally satisfactory but underline a need for future training sessions focused on practical aspects.

Haemodynamic changes and vasopressin release are not consistently associated with carbon dioxide pneumoperitoneum in humans.

BACKGROUND: Conflicting haemodynamic changes, suggested to be caused by vasopressin release, have been reported during carbon dioxide (CO2) pneumoperitoneum. However, peritoneal stimulations including open surgery cause both a systemic vasopressor response and a vasopressin release, which are suppressed by opiate administration. Also, a decreased venous return of blood to the heart causes vasopressin release. Furthermore, previous haemodynamic assessments of laparoscopic surgery have been conducted using various anaesthetic regimens, which are likely to have caused various haemodynamic effects. We hypothesised that intraoperative haemodynamic and/or humoral changes would not be observed in association with laparoscopic surgery provided that, (a) normovolaemia is continuously maintained using transoesophageal echocardiographic (TEE) assessment, and (b) adequate depth of general anaesthesia is continuously maintained by bispectral index (BIS) monitoring and high plasma Ievel opiate administration. METHODS: Twenty ASA 1 women undergoing laparoscopic surgery received 10 ml. kg-1 lactated Ringer's solution and thereafter were randomly allocated to receive intraoperatively either 8 ng. ml-1 or 4 ng. ml-1 plasma remifentanil concentrations while BIS was maintained at 50+/-5 by isoflurane alteration. The group receiving 4 ng. ml-1 remifentanil was used as control. Expired CO2 was maintained within a 32-38 kPa range throughout the investigation. Complete TEE haemodynamic investigation was performed before pneumoperitoneum (PP) (T1), and during PP horizontal (T2), with a head-up tilt (T3), with a head-down tilt (T4), horizontal (T5), and PP released (T6). Plasma vasopressin, epinephrine and norepinephrine levels were measured at T1, T3, and T6. ANOVA, Student's t-test and Mann-Whitney U-test were used for statistical analysis. RESULTS: Haemodynamic indices and humoral values did not change significantly within and between remifentanil groups throughout the investigation (all P<0.05). CONCLUSION: Continuous adequate depth of anaesthesia and normovolaemia may have prevented both a humoral and a haemodynamic response, initiated in the peritoneum by the contact with CO2 in previous investigations.