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Renal transplantation is the best option for patients with end stage renal failure, since it significantly improves their duration and quality of life. The number of patients waiting for a kidney transplant continues to increase while the overall rate of organ procurement in France is stable. The graft shortage is worsening, as is the waiting time on list. Identifying the causes of this crisis and discussing the various options for addressing the kidney graft shortage is the aim of this talk. Among the solutions: (i) improving identification of potential donors through a national and hospitals policy to promulgate organ donation and understanding better the grounds for refusal; (ii) using infusion machines for all grafts with extended criteria; (iii) developing transplantation programs from deceased donors after cardiac arrest; (iv) developing transplantation programs from living donors.

Tocilizumab (TCZ) is a monoclonal antibody that inhibits the interleukin 6 (IL-6) signalling pathway. This treatment is extremely effective in rheumatoid arthritis (RA), which may well be accompanied by serious infections presenting misleading clinical pictures. Herein we report a case of a typical bacterial dermo-hypodermitis in a female patient treated with TCZ.An 80-year-old woman treated with methotrexate (MTX) and TCZ for RA presented dermo-hypodermitis on her left leg 8 days after receiving her 13th infusion of TCZ. She exhibited neither fever nor biological inflammatory syndrome. Oral amoxicillin (3g/d) was initiated on an outpatient basis. Two weeks later, the patient was apyretic and her laboratory results were normal, although local inflammatory signs persisted. TCZ infusion was postponed and she was given intravenous amoxicillin (4g/d) for 2days, followed by oral amoxicillin, resulting in rapid recovery. Subsequent courses of TCZ were administered without incident.During the course of treatment with TCZ, this patient presented delineated bacterial cellulitis in the form of erysipelas, which was noteworthy on account of the absence of fever and of biological inflammatory syndrome. While there have been reports of severe cases of cellulitis during TCZ treatment, to our knowledge, there have been none of erysipelas. Attenuation of local and systemic inflammatory symptoms is widely reported, and is directly associated with the anti-IL-6 action of TCZ. Patients with RA are especially susceptible to opportunistic or severe infections as a result of the disease itself and of associated treatments, and increased vigilance is called for with regard to infections that may be transformed and potentially more severe as a result of TCZ.

Within the cystic fibrosis patients' home care, EMERAA network ("Together against Cystic fibrosis in Rhone-Alpes and Auvergne") organizes parenteral antibiotics cures at home prepared in elastomeric infusion devices by hospital pharmacies. However, patients and nurses found that the durations of infusion with these devices were often longer than the nominal duration of infusion indicated by their manufacturer. This study aimed to identify the potential different causes in relation to these discordances.Three hundred and ninety devices of two different manufacturers are tested in different experimental conditions: three antibiotics each at two different doses, duration of cold storage (three days or seven days) or immediate tests without cold storage, preparation and storage of the solution in the device (protocol Device) or transfer in the device just before measurement (protocol Pocket).All tests highlighted a longer flow duration for devices prepared according to the protocol Device versus the protocol Pocket (P=0.004). Flow duration is increased in the case of high doses of antibiotics with high viscosity such as piperacilline/tazobactam.The results of this in vitro study showed the impact of: (1) the time between the filling of the device and the flow of the solution; (2) cold storage of elastomeric infusion devices; (3) concentration of antibiotics and therefore the viscosity of the solution to infuse.It is therefore essential that health care teams are aware of factors, which may lead to longer infusion durations with these infusion devices. When the additional time for infusion remain acceptable, it should be necessary to inform the patient and to relativize these lengthening compared to many benefits that these devices provide for home care.

This study aimed to determine the influence of the age and the level of malaria transmission on the clinical and biological expression of severe malaria in children.A prospective descriptive study was conducted in nine referral hospitals in Kinshasa. A total of 1350 children, less than 15years old and hospitalized for severe malaria, were progressively included in the study between January and November 2011.The majority of these children (74.5%) were less than 5years of age. Major syndromes were severe anemia (11.4%), cerebral malaria (27.1%), and respiratory distress (20.5%). Severe anemia and cerebral malaria were associated with the age of the child and not the area transmission. On the other hand, respiratory distress was associated with high malaria transmission areas (P0.05). After adjustment, these associations were maintained. High malaria lethality was observed in the group of children aged 12-59months (11.6%) and those from areas of high malaria transmission (8.4%).The child's age and level of transmission are associated with certain severe types of childhood malaria. Early and appropriate support would reduce the most fatal consequences associated with severe childhood malaria.

Continuous sedation is an acknowledged medical practice in the management of refractory symptoms at the end of life. Guidelines and recommendations have been proposed in palliative care. This paper presents the state-of-the-art (definitions, indications, technical aspects) on continuous sedation followed by an ethical reflection essentially based on the "double effect" principle, on the impact on life expectancy and the assimilation of continuous sedation as a "natural death". Distinction between continuous sedation and legal euthanasia is clarified.

Bivalirudin, a direct thrombin inhibitor, demonstrated an improvement in the prognosis of acute coronary syndromes by a decrease in major bleeding complications. This observational study evaluated inhospital outcome of patients with acute myocardial infarction treated by prehospital bivalirudin before primary angioplasty.We included, from June 2010 to June 2012, all patients with acute myocardial infarction receiving prehospital bivalirudin with bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg per hour until the arrival in the catheterization laboratory. Bivalirudin was possibly continued after primary angioplasty.We included 152 patients aged 57.6±11.6 years. A prehospital 60mg loading dose of prasugrel was given in 77% of patients. Coronary angiography with radial access (77.6%) was performed before a successful angioplasty in 97.3% of cases. The bivalirudin infusion was continued after the procedure in 81.6% of patients. Inhospital outcome showed two deaths (1.3%) and two re-infarctions (1.3%) of which one was related to the single acute stent thrombosis (0.6%). Major bleeding complications were limited irrespective of the Gusto (0.6%), Timi (0.6%) or Horizons-MI (4.6%) classification. Bleeding complications rate was similar when bivalirudin was followed or not after primary angioplasty.The use of bivalirudin in the prehospital setting for primary angioplasty seems to be effective and safe about ischemic and bleeding complications during the inhospital outcome.

A reflection on perfusion and the use of flow control systems was carried out in the Hospices Civils, Lyon (69) in 2008. This initiative was conducted over 3 years by the Pharmacists, the Central Care Directorate and the Committees for drugs and sterile medical devices. In particular, recommendations for the use of flow regulators were issued and their impact was evaluated at 8 months of their distribution by a survey on nursing practices.

In the intensive care environment, technology is omnipresent to ensure the monitoring and the administration of critical drugs to unstable patients. Since the early 2000's computerized physician order entry (CPOE), bar code assisted medication administration (BCMA), "smart" infusion pumps (SIP), electronic medication administration record (eMAR) and automated dispensing systems (ADS) have been recommended to reduce medication errors. About ten years later, their implementation rises but remains modest. The objective of this study is to determine the impact of these technologies on the rate of medication errors (ME) in adult intensive care. CPOE allows a strong and significant reduction of ME, especially the least critical ones. Only when adding a clinical decision support system (CDSS), CPOE could allow a reduction of serious errors. Used alone, it could even increase them. The available studies do not have the sufficient power to demonstrate the benefits of SIP or BCMA on ME. However, these devices, reveal practices, such as overriding of alerts. Power or methodology problems and conflicting results do not allow to determine the ability of ADS to reduce the incidence of ME in the intensive care. The studies, investigating these technologies, are not very recent, of limited number and present lacks in their methodology, which does not allow to determine whether they can reduce the incidence of MEs in the adult intensive care. Currently, the benefits appear to be limited which may be explained by the complexity of their integration into the care process. Special attention should be given to the communication between caregivers, the human-computer interface and the caregivers' training.

The aim of the study is to analyse the effects of ropivacaïne on a pyrolytic implant in bone surgery. Ten rats were operated with a pyrolytic implant placed at the hip after femoral head resection: five cases with continuous infusion of ropivacaïne and five cases with continuous infusion of sterile water. Six days after, all the implants were analysed: weight, length, width, thickness and global design. This work showed that ropivacaïne can be use as continuous infusion with pyrolytic implant. Other studies in human surgery are necessary.

An assessment of practices and available medical devices during the treatment of a massive haemorrhage has been realised in the shock unit of our hospital.Parameters influencing transfusion flow rate have been identified. Medical devices and equipment to accelerate the flow rate were analyzed on the basis of manufacturers' data and users opinion in relation with their practices.The system, from blood bags to venous access, influences flow rate: red blood cell viscosity, catheter and pressure gradient. Three types of acceleration systems are available: accelerated transfusion set, pressure cuff with a gravity blood IV set and fast-flow fluid warmers. Their benefits and disadvantages are presented and discussed.Maximum flow rates noted by manufacturers are not the real values because some parameters such as venous catheter diameter (limitative factor) and the red blood cell viscosity (diluted or not) are not considered. The choice of an infusion system is mainly based on the technical capacities (flow rate fluctuations, pressure gradient on blood bags, warming, air purging), practical modalities of use (medical devices and assembly) and cost. The pressure cuff with transfusion gravity set should be limited to non-critical situations or during the assembly of the fast flow fluid warmers (but no warming fluids, no air embolism prevention). The accelerated transfusion set is not the best option for a shock unit because it needs an operator permanently. The fast-flow fluid warmers are recommended for all types of massive haemorrhages, they are more secure but they require a long time to be assembled.

To assess the usefulness and the feasibility to use a software supervising continuous infusion rates of drugs administered with pumps in ICU.Follow-up of practices and inquiry in three intensive care units.Guardrails software(TM) of reassurance of the regulations of the rates of pumps (AsenaGH, Alaris).First, evaluation and quantification of the number of infusion-rates adjustments reaching the maximal superior limit (considered as infusion-rate-errors stopped by the software). Secondly, appreciate the acceptance by staffs to such a system by a blinded questionnaire and a quantification of the number of dataset pumps programs performed with the software.The number of administrations started with the pumps of the study in the three services (11 beds) during the period of study was 63,069 and 42,694 of them (67.7 %) used the software. The number of potential errors of continuous infusion rates was 11, corresponding to a rate of infusion-rate errors of 26/100,000. KCl and insulin were concerned in two and five cases, respectively. Eighty percent of the nurses estimated that infusion-rate-errors were rare or exceptional but potentially harmful. Indeed, they considered that software supervising the continuous infusion rates of pumps could improve safety.The risk of infusion-rate-errors of drugs administered continuously with pump in ICU is rare but potentially harmful. A software that controlled the continuous infusion rates could be useful.

At the end of the seventy, we saw the reconstructive microsurgery developed to such an extent that it became a new and an independent surgical specialty. The development of the microsurgical instrumentation and the description of the surgical anatomy allowed the application of this technology to the most complex plastic reconstructions and particularly to the replantation of the amputated digits, especially the very distal digital amputations. Nowadays, the indications of digital replantation are well-defined according to numerous parameters conditioning the anatomical result and the functional outcome. It is well-known that the replantation of the amputated digit should be realized as soon as possible with optimal conditions of digital hibernation during the patient transport. In spite of that technical progress, the failure rate is still relatively important. The causes are sometimes recognizable and connected to technical defection, such as a non permeable vascular anastomosis, bad hemodynamics conditions or an insufficient anticoagulation, while in certain cases, the digital ischemia occurs in spite of permeable and technically successful arterial anastomosis. We then consider a "no reflow phenomenon". It corresponds to the constitution of vascular microthrombi which will block the arteriolar network. Those microthrombi are inaccessible to the microsurgical techniques and their treatment remains medical by intra-arterial infusion of antithrombotic agents. Through our series of fifteen digital replantations, having suffered a "no reflow phenomenon", we are going to present the fibrinolytic protocol we used and the promising results we obtained. All our patients were victims of traumatisms associating avulsions and crush injuries mechanisms. The conditions of preservation of the amputated digits were all quite unfavourable: 1) the amputated digit soaked in water in 5 cases; 2) the amputated fingers underwent a long-term "warm ischemia" in three cases, going up to 13 hours for one of them; 3) the amputated digits were completely frozen in six cases; 4) and one amputated finger was correctly hibernated but for too long a period (8 hours). The signs of ischemia appeared very prematurely in the first minutes after the microvascular revascularisation in ten cases, and in average within three hours postoperatively in the other five cases, with extreme cases going from 2 up to 6 hours. As soon as the diagnosis of "no reflow phenomenon" was confirmed, an intra-arterial catheter was fixed. The radial axis was chosen as the arterial infusion way and approached at the level of the pulse groove. The antithrombotic protocol included a flash of 50,000 UI of urokinase, 36 ml of lidocaïne 1% and 40 mg of enoxaparine, followed by an electric syringe infusion the first six hours with 150,000 UI of urokinase, 36 ml of lidocaïne 1% and 40 mg of enoxaparine at 6 cc/h speed. The urokinase was then interrupted but the intra-arterial infusion maintained with 72 ml of lidocaïne 1% and 80 mg of enoxaparine for 24 hours, at a 3 cc/h speed, and this for ten days. In 12 cases, the "no reflow phenomenon" was able to be raised and the digital vascularization restored. The success rate is very encouraging (80%) and it turns this protocol into a precious ally of the digit replantation microsurgery and an effective therapeutic means way against the "no reflow phenomenon".

The infusion of vasoactive drugs in preterm babies using syringe pumps can be complicated by important variations in the infusion rate.1) to assess the time between pump start and the actual presence of a substance in the circulation, when using slow rates; 2) to evaluate the effects of changes in the main infusion rate on substance rates infused on the same line.We used 10% glucose to mimic vasoactive drugs. The main infusion consisted of saline, and both were infused on the same line using syringe pumps. Glucose concentration was measured at the end of the line.The time between pump start and the actual infusion of glucose depended on syringe volume and on the adjustment of the syringe in the pump. There was a transient increase in glucose rate when the main rate increased, and a transient decrease when the main rate decreased.To minimize the time before a substance is actually infused, one should use low volume syringes and correctly adjust the syringe in the pump. Moreover, when a steady infusion rate is necessary, one should avoid variations in the main infusion rate.

We report the case of a 67-year-female patient treated with a postoperative patient controlled analgesia using an Abbott Gemstar pump for after nephrectomy. In the postanaesthesia care unit, fifteen minutes after connecting with of the pump (which bag contained 100 mg of morphine) to the patient, respiratory arrest occurred. A morphine overdose was caused by uncontrolled delivery of the entire bag contents by free flowing due only to gravity. The patient was resuscitated immediately, and had uneventful recovery. This incident was the result of multiple misuse: one misconnection of the tubing between morphine bag and the patient thus shunting the antisiphon valve, and two an improper secured PCA cassette in an open position not detected by the pump. The tubing of these pumps and the software were subsequently modified by Abbott, which should reduce the risk of recurring incident. This accident points out that vigilance must remain rigorous in spite of widespread routine use of PCA.

Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

To evaluate the risk of retrograde embolization of flush solution in neonates and infants with routinely used electronic syringe pumps and infusion bag pump flush systems.With hospital Ethical Committee approval we studied intubated neonates and infants with a 24-GA radial arterial cannula. Fast flush boluses were delivered from the infusion bag pump flush system by opening the flow regulating device for two seconds at bag pump manometre pressures of 100, 200 and 300 mmHg. In the syringe pump flush system, fast flush bolus volumes of 0.5, 1.0, 1.5 and 2.0 mL were programmed on the electronic syringe pump and released by opening the flow regulating device for two seconds. A 12-MHz ultrasonic probe placed in the jugular fossa was used to detect white bubbles indicating retrograde embolization of flush solution into the ipsilateral subclavian and common carotid artery.Sixteen patients, aged from 1-105 days (median 22 days) were studied. In all patients retrograde embolization into the subclavian artery was detected at syringe pump bolus volumes of 0.5-1.5 mL and at 100-200 mmHg bag pump pressure. In nine of the 16 patients a positive signal was detected in the common carotid artery with 1.5-2.0 mL syringe pump bolus volumes and at 200-300 mmHg bag pump pressure.In neonates and infants, the standard practice of arterial fast bolus flushing using syringe pump and bag pump flush systems causes retrograde embolization of flush solution into the central arterial and even into the cerebral circulation. The mandatory limitation of fast flush bolus volumes and manometre pressures is urgent in order to reduce retrograde embolization of flush solution and the associated risks in these small patients.

To identify the factors that threaten patient safety when using patient-controlled analgesia (PCA) and to obtain an evidence-based estimate of the probability of death from user programming errors associated with PCA.A 19-yr-old woman underwent Cesarean section and delivered a healthy infant. Postoperatively, morphine sulfate (2 mg bolus, lockout interval of six minutes, four-hour limit of 30 mg) was ordered, to be delivered by an Abbott Lifecare 4100 Plus II Infusion Pump. A drug cassette containing 1 mg.mL(-1) solution of morphine was unavailable, so the nurse used a cassette that contained a more concentrated solution (5 mg.mL(-1)). 7.5 hr after the PCA was started, the patient was pronounced dead. Blood samples were obtained and autopsy showed a toxic concentration of morphine. The available evidence is consistent with a concentration programming error where morphine 1 mg.mL(-1) was entered instead of 5 mg.mL(-1). Based on a search of such incidents in the Food and Drug Administration MDR database and other sources and on a denominator of 22,000,000 provided by the device manufacturer, mortality from user programming errors with this device was estimated to be a low likelihood event (ranging from 1 in 33,000 to 1 in 338,800), but relatively numerous in absolute terms (ranging from 65-667 deaths).Anesthesiologists, nurses, human factors engineers, and device manufacturers can work together to enhance the safety of PCA pumps by redesigning user interfaces, drug cassettes, and hospital operating procedures to minimize programming errors and to enhance their detection before patients are harmed.

To evaluate what could be the benefit in terms of alarm suppression, of a new syringe pumps system, which allows automatic relay without alarms.We have prospectively recorded the nature and the mode of relay of all syringe pumps for administration of drugs to patients in two ICU. The perfusion regimen was studied in 61 patients over the complete duration of their stay in two ICU. Alarms were also recorded in one ICU room, over 13 days consecutive. The records were processed off-line with an automatic detection-recognition system in order to assess the origin of each alarm. Accordingly, the amount of alarm corresponding to monitor, ventilator and syringe pumps was computed.We found that syringe pumps, which would provide automatic relays without alarm, would suppress 17% of alarms in ICU and automatize 65% of the relay procedures, which are usually performed often in emergency, on response to the end of perfusion alarm.New syringe pumps allow both reduction of alarms in ICU and a better management of nurse workload. Indeed syringe relay can be planned in advance.

To analyze retrospectively the data base of the French national vigilance reporting system concerning infusion devices during the year 1998.Each report has been reviewed and classified, except implantable catheter ports.The study included 309 reports. Among them, 28% concerned infusion pumps and 72% single use devices, i.e. catheters, infusion lines, taps, connectors, etc. We observed six deaths and 23 severe incidents. Only 25% of devices could be formally investigated by manufacturers. The origins of incidents were very different between infusion pumps and single use devices. The first showed simple failures, software errors, maintenance omissions or errors, and problems related to obsolescence of the device. The second revealed manufacturer quality insurance failures, design and utilization errors, and problems related to the technique itself rather than device.Our findings are similar to the few data available in international literature. They address the need to obtain an adequacy between the performances of devices which vary with generations of devices and the clinical risks: newest and safest devices should be preferred for the infusion of the most critical drugs.

In the past, the treatment of benign uterine lesions required, in many instances, a hysterectomy. These days, most cases can be successfully treated by hysteroscopy. To be reliable, this technique must lead to a significant reduction in the number of hysterectomies performed for benign uterine lesions. The electroresection technique is preferred to that using the Nd-YAG laser because of its lower cost and its equivalent efficacy. By using the uterine perfusion pump device, the risk of resorption syndrome can be reduced to its minimum. Submucosal myomas1 cm, benign endometrial hyperplasia and adenomyosis are the commonest benign lesions treated. Dysfunctional uterine bleeding can also be treated by an endometrectomy. A preoperative workup includes a transvaginal ultrasound and a biopsy. This ensures that only benign lesions that are accessible to a hysteroscopy will be submitted to this technique and that no cases of endometrial cancer or atypical hyperplasia would be ignored. This study presents 270 cases of operative hysteroscopy with a follow-up to 4 years. 82.8% of myomatous lesions were treated with success. The results for patients with benign endometrial polyps or benign endometrial hyperplasia are also excellent with only 4.6% and 5.6% rate of secondary surgery respectively. Adenomyosis does not appear to be a good indication for hysteroscopy as only 37% of patients did not need a definitive hysterectomy. Rates of operative complications (post-operative bleeding, uterine perforation, resorption syndrome and difficulty of access) are acceptable and get less frequent as the surgeon experience increases.

Target-controlled infusion (TCI) is a new delivery system for i.v. anaesthetic agents with which the anaesthetist targets a plasma drug concentration to achieve a predetermined effect. With this system, the tedious task of calculating the amount of administered drug required to achieve the target concentration is left in charge of a microprocessor which commands the infusion device. TCI has long been used only by a few research teams, but this year a much wider field opens to this delivery system through marketing of Diprifusor, a TCI system specifically designed for administration of propofol in everyday practice. This article describes the rationale for administering i.v. agents through TCI delivery systems, the pharmacokinetic basis of TCI, the regulations and a broad overview of clinical applications, both recent and yet to come.

Adaptive dosing of cisplatin (CDDP) results in reduced haematological and renal toxicity but it has never been clearly shown that it affects the tumoral response rate. Before undertaking a clinical randomized study of CDDP monitoring versus standard dose, a comparative study was performed between a new software dedicated to the interactive adjustments--the AJI software--and the APIS software for clinical pharmacokinetics which incorporates a bayesian procedure and a population information computed according to a three compartment model. CDDP was administered by continuous infusion at variable rates with a controlled flow pump during four days in order to reach the target of 1.3 mg/L at the end of the first day, and to maintain this level during the whole treatment. This study was carried out on two groups of patients. Group 1 (12 patients; 27 courses) received CDDP with sequential flow rates in order to obtain a population information to be used with AJI. For patients in group 2 (14 patients; 26 courses), doses (flows) were adapted in a prospective study using the AJI software two to three times the first day, then daily. They could have been adapted (retrospective study) after platin pharmacokinetic parameters identification by APIS. The dosage recommendations proposed by APIS the first day, from 12 hours to 24 hours, to reach the target of 1.3 mg/L at 24 hours, and then daily up to D4 (AAPT at Di) to maintain this level were compared to those which were really administered during the interactive treatment (DA at Di). There were no statistically significant difference for D2, D4 and for the total dose (118.7 +/- 20.1 mg and 118.5 +/- 45.1 mg). The difference was statistically significant for D1 and D3 (P0.05). The inter-individual variability was less important with AJI (CV = 16.9% for DA total) than with APIS (CV = 38.0% for ADAPT total). The platin pharmacokinetic parameters identified the first day by APIS were not statistically different from those identified from the whole treatment for clearance (5.92 and 5.63 l/d) and Vtotal 87.8 and 93.1 L); the difference was statistically significant for Vinitial (34.7 and 42.5 L; P0.05) and the terminal half-life (13.1 and 15.5 days; P0.05).

To assess the benefit of ketamine addition to a morphine-clonidine-lidocaine mixture administered continuously by the intrathecal route for the treatment of cancer pain.Case series analysis.Four patients experiencing cancer pain with nociceptive and neuropathic components were treated with a continuous intrathecal administration of a mixture of ketamine (10 mg)-morphine (1-20 mg)-clonidine (30 micrograms)-lidocaine (20 mg) in 12 mL of normal saline, injected daily with an infusor (Baxter) pump. This treatment, associated with oral administration of sustained release morphine (SRM), was extended over 35 to 58 days, until the death of the patients.Either the secondary addition of ketamine to the morphine-clonidine-lidocaine mixture after the 40th and 15th days of treatment in patients no 1 and 2 respectively, because of a loss of efficiency of the mixture, or the immediate administration of the association of the four agents in patients no 3 and 4 provided efficient analgesia, unchanged over time, without significant adverse effects and allowed a decrease of the SRM doses.Ketamine by intrathecal route potentiates analgesia obtained with morphine-clonidine and lidocaine, while impeding the development of a tolerance vis-à-vis the former.

Circadian (about 24 h) changes modulate cellular metabolism and proliferation in healthy tissues. As a result, the extent of toxicity of cancer chemotherapy varies by 50% or more according to dosing time in mice or rats. These experimental data led to test the principle of adapting chemotherapy delivery to circadian rhythms--so-called "chronotherapy"--in cancer patients. Clinical trials first aimed to assess toxicities and maximal tolerated dose of chronotherapy schedules. Programmable-in-time pumps became the indispensable tool for reliably testing this principle in a large enough patient population and without any need for hospitalization. Results from randomized clinical trials have indicated that chronotherapy allowed to increase dose intensity (DI, a secondary criterion in these trials) by 13 to 45% as compared to injecting the drug at another time (doxorubicin, cisplatin) or according to a flat rate (5-fluorouracil, floxuridine, oxaliplatin). A non-randomized trial further suggested this principle would also apply to cytokine delivery (interferon alpha). Two consecutive randomized trials have revealed that chronotherapy-related increase in 5-FU DI was further associated with a 20% increase in response rate of patients with metastatic colorectal cancer to the 3-drug association that was used (5-FU, folinic acid and oxaliplatin). In a subsequent phase II trial 5-FU daily dose and 3-drug treatment frequency were increased in 50 patients with this disease. Such intrapatient dose escalation protocol also disclosed a positive correlation between DI of 5-FU and response. New anticancer drugs should benefit from this approach so that both their clinical safety and patient's quality of life are improved, through ambulatory administration.

Intravenous patient-controlled analgesia (PCA) is an effective technique to relieve most forms of acute postoperative pain. However it is not easy to apply. An adequate training of the nursing staff has been for a safe and successful use in the recovery room and the wards as well. Our study was aimed to assess such a training. The most common errors during training period included the incorrect preparation of syringes and the inadequate use of i.v. lines. Errors in programming were spontaneously rectified by using a special procedure. Specific acute pain nurse teams were trained. To optimize the pump use and promote safety and efficacy, special protocols and procedures were devised. PCA is now accepted as a normal nurse procedure. There is no longer any resistance against the introduction of PCA in the wards. Training of nursing staff for the use of PCA devices is essential in order to avoid "human errors". PCA has become routine for the management of postoperative pain.

Administration of propofol using standard syringe pumps has become routine in anaesthesia. The marketing of syringe pumps adapter for anaesthesia (high flow rate enabling a bolus injection and a slower rate for maintenance), allows an easier setting up of total intravenous anaesthesia. Computer-aided infusion of propofol will undoubtedly expand in the near future, as a result of the forthcoming marketing of computer-controlled infusion pumps and of improvement in the recognition of accurate individual pharmacokinetic parameters. This computer-aided infusion will be based on a blood concentration criterion, and no longer on a dosage regimen given to the patient. A closed loop regulatory system remains in the domain of research.

Intensive therapy includes continuous delivery of drugs with infusion pump. This article describes an infusion rate computing programme using a Macintosh micro-computer and the HyperCard 2 software. The latter permits the classification of data onto cards collected in stacks. The card that is displayed when the programme is launched shows fifteen buttons assigned to various drugs. Click upon a button opens the corresponding card which displays the presentation of the drug and suggests a dilution. The next step associates input of patient's weight into the appropriate field and a click on the main button. A display then indicates for various standard dosages, the corresponding rate of infusion in mL.h-1 and the daily consumption of the drug. In order to avoid casual or voluntary changes of the setting, soft securities have been inserted in the programme.