100 Hz-5 s tetanic stimulation to illustrate the presence of "residual paralysis" co-existing with accelerometric 0.90 train-of-four ratio-A proof-of-concept study.

BACKGROUND: An acceleromyographic train-of-four (TOF) ratio of 0.90 at extubation does not prevent postoperative pulmonary complications in surgical patients receiving non-depolarising muscle relaxants. This recent observation suggests that a more selective neuromuscular transmission monitoring parameter is mandatory to detect more precisely any remaining residual paralysis. The aim of our proof-of-concept study was to evaluate, in patients receiving rocuronium, the degree of 100-Hz, 5-s tetanic fade present when the acceleromyographic TOF ratio has recovered to 0.90. METHODS: Twenty adult patients scheduled for surgery under general anaesthesia were included. Before anaesthesia induction, a TOF-Watch SX™ and a VISUAL-ITF© (a prototype monitor for recording isometric force) were positioned on both hands. After induction but before rocuronium injection, a 100-Hz, 5-s tetanus (TET0) was delivered to both ulnar nerves. Thereafter, TOF stimulations every 15 s were delivered to both arms until a TOF ratio > 0.90 was recorded; then, a 100-Hz, 5-s tetanus (TET1) was recorded on the VISUAL-ITF© monitor. The values of the tetanic parameters (force) recorded at TET0 and TET1 were compared using a Wilcoxon rank sum test. RESULTS: Compared to TET0, tetanic parameters of TET1 were significantly lower (median [range]): maximal force 36.4 [19.2-82.6] vs. 25.5 [5.0-42.4] Newton (p < 0.005); residual force 36.2 [18.2-82.0] vs. 5.5 [0.20-38.3] Newton (p < 0.0001) and residual force/maximal force ratio 0.98 [0.89-0.99] vs. 0.17 [0.03-0.90] (p < 0.0001). CONCLUSION: Our results confirm that even when the acceleromyographic TOF ratios have recovered to above 0.90, the contralateral 100-Hz, 5-s tetanic stimulus may show tetanic fade characteristic of residual neuromuscular block, and may help improve the safety of tracheal extubation.

Observance of preoperative clear fluid fasting in pediatric anesthesia: oral and written information versus text message information. A before-and-after study.

INTRODUCTION: Prolonged fasting before surgery is common in pediatrics. In the literature, it is responsible for hypotension, irritability and postoperative nausea and vomiting. Despite clear instructions given during the preanesthetic consultation, fasting rules are respected in only 30%-40% of cases. We aimed to evaluate the benefit of sending a text message the day before surgery to improve the parents' observance of fasting rules. METHODS: We conducted a before-and-after study at the University Hospital of Poitiers. From August to October 2018, 172 parents of children under 15 years of age scheduled for all types of surgery were enrolled into two groups according to the period: the control group with parents receiving information on preoperative fasting rules during the preanesthetic consultation several days before surgery, and the text message group, receiving the same information during consultation plus a text message the day before the surgery. RESULTS: There was a difference in observance of clear fluid fasting instructions (between 2 and 3 h before the admission at hospital) in favor of the text message group 33% versus 92% OR 29.2 (10.9-95.2) p < 0.001, and in average fasting time for clear fluids 8.7 h ± 4.8 h vs. 4.3 h ± 2.4 h (p < 0.001). CONCLUSION: Sending of a reminder text message to the parents the day before the surgery resulted in a significant increase in observance of fasting rules in children undergoing scheduled surgery.

Guidelines on muscle relaxants and reversal in anaesthesia.

OBJECTIVES: To provide an update to the 1999 French guidelines on "Muscle relaxants and reversal in anaesthesia", a consensus committee of sixteen experts was convened. A formal policy of declaration and monitoring of conflicts of interest (COI) was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE®) system to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making strong recommendations based on low-quality evidence were stressed. Few of the recommendations remained ungraded. METHODS: The panel focused on eight questions: (1) In the absence of difficult mask ventilation criteria, is it necessary to check the possibility of ventilation via a facemask before muscle relaxant injection? Is it necessary to use muscle relaxants to facilitate facemask ventilation? (2) Is the use of muscle relaxants necessary to facilitate tracheal intubation? (3) Is the use of muscle relaxants necessary to facilitate the insertion of a supraglottic device and management of related complications? (4) Is it necessary to monitor neuromuscular blockade for airway management? (5) Is the use of muscle relaxants necessary to facilitate interventional procedures, and if so, which procedures? (6) Is intraoperative monitoring of neuromuscular blockade necessary? (7) What are the strategies for preventing and treating residual neuromuscular blockade? (8) What are the indications and precautions for use of both muscle relaxants and reversal agents in special populations (e.g. electroconvulsive therapy, obese patients, children, neuromuscular diseases, renal/hepatic failure, elderly patients)? All questions were formulated using the Population, Intervention, Comparison and Outcome (PICO) model for clinical questions and evidence profiles were generated. The results of the literature analysis and the recommendations were then assessed using the GRADE® system. RESULTS: The summaries prepared by the SFAR Guideline panel resulted in thirty-one recommendations on muscle relaxants and reversal agents in anaesthesia. Of these recommendations, eleven have a high level of evidence (GRADE 1±) while twenty have a low level of evidence (GRADE 2±). No recommendations could be provided using the GRADE® system for five of the questions, and for two of these questions expert opinions were given. After two rounds of discussion and an amendment, a strong agreement was reached for all the recommendations. CONCLUSION: Substantial agreement exists among experts regarding many strong recommendations for the improvement of practice concerning the use of muscle relaxants and reversal agents during anaesthesia. In particular, the French Society of Anaesthesia and Intensive Care (SFAR) recommends the use of a device to monitor neuromuscular blockade throughout anaesthesia.

A comparison between the flexor hallucis brevis and adductor pollicis muscles in atracurium-induced neuromuscular blockade using acceleromyography: A prospective observational study.

BACKGROUND: Neuromuscular blockade (NMB) monitoring is essential to avoid residual NMB. While the adductor pollicis is the recommended site for monitoring recovery, it is not always accessible. The flexor hallucis brevis could be an interesting alternative. OBJECTIVE: The aim of our study was to compare NMB onset and recovery at both sites. DESIGN: Prospective observational study. SETTING: Operating rooms at the University Hospital of Poitiers, France. PATIENTS: Sixty patients scheduled for surgery under general anaesthesia with neuromuscular blocking agents were enrolled from January 2016 to September 2017. Data from 56 patients were finally analysed. Among these, 11 patients received pharmacological reversal with neostigmine and atropine before emergence from anaesthesia. INTERVENTION: After atracurium injection, NMB onset and recovery at the adductor pollicis and flexor hallucis brevis were monitored simultaneously. MAIN OUTCOME MEASURES: The time to NMB onset, defined as a train-of-four (TOF) count equal to 0, and the times to NMB recovery: TOF = 1, TOF = 4, T4/T1 ratio = 0.75 and T4/T1 ratio more than 0.90. RESULTS: NMB onset was significantly slower at the flexor hallucis brevis with a mean onset time of 4.4 ±â€Š1.5 versus 3.7 ±â€Š1.2 min at adductor pollicis (P = 0.0001). Recovery to TOF = 1 was significantly slower at flexor hallucis brevis. No difference was found for TOF = 4. The full recovery of NMB (T4/T1 > 0.90) was significantly faster at flexor hallucis brevis with a mean time to recovery of 59.5 ±â€Š9.9 versus 64.5 ±â€Š10.7 min at adductor pollicis (P < 0.0001), a difference of 4.9 min between both sites. This difference was not present after pharmacological reversal with a mean time to recovery of 53.0 ±â€Š12.2 min at flexor hallucis brevis versus 54.0 ±â€Š12.4 min at adductor pollicis (P = 0.28). However, NMB onset and recovery did not follow the same pattern in individual patients. CONCLUSION: Flexor hallucis brevis could be an interesting alternative site for NMB monitoring when the adductor pollicis is not accessible. However, in the absence of pharmacological reversal, monitoring at the hallucis brevis muscle should be used with caution for the detection of residual paralysis. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02825121).

How to optimize neuromuscular blockade in ambulatory setting?

PURPOSE OF REVIEW: The purpose of this review is to discuss the optimal use of neuromuscular blocking agents (NMBA) during ambulatory surgery, and to provide an update on the routine use of neuromuscular monitoring and the prevention of residual paralysis. RECENT FINDINGS: The number of major surgical procedures performed in ambulatory patients is likely to increase in the coming years, following the development of laparoscopic and thoracoscopic procedures. To successfully complete these procedures, the proper use of NMBA is mandatory. The use of NMBA not only improves intubating conditions but also ventilation. Recent studies demonstrate that NMBA are much more the solution rather than the cause of airway problems. There is growing evidence that the paralysis of the diaphragm and the abdominal wall muscles, which are resistant to NMBA is of importance during laparoscopic surgery. Further studies are still required to determine when deep neuromuscular block [posttetanic count (PTC) < 5] is required perioperatively. There is now a consensus to use perioperatively neuromuscular monitoring and particularly objective neuromuscular monitoring in combination with reversal agents to avoid residual paralysis and its related morbidity (e.g. respiratory complications in the PACU). SUMMARY: Recent data suggest that it is now possible to obtain a tight control of neuromuscular block to maintain optimal relaxation tailored to the surgical requirements and to obtain a rapid and reliable recovery at the end of the procedure.

Intra-operative cutaneous temperature monitoring with zero-heat-flux technique (3M SpotOn) in comparison with oesophageal and arterial temperature: A prospective observational study.

BACKGROUND: Continuous monitoring of core temperature is essential during major surgery as a way of improving patient safety. Oesophageal probes or specific arterial catheters are invasive methods used in this setting. A new noninvasive device based on zero-heat-flux (ZHF) technique (SpotOn) seems promising but has been poorly investigated during rapid core temperature changes (RCTC). OBJECTIVE: To assess the accuracy of a SpotOn sensor vs. an oesophageal probe or specific arterial catheter during a slow change in core temperature of less than 1 °C within 30 min and RCTC ≥ 1 °C within 30 min. DESIGN: Prospective observational study. SETTING: Operating rooms at the University Hospital of Poitiers, France. PATIENTS: Fifty patients scheduled for major abdominal surgery under general anaesthesia were enrolled from June 2015 to March 2016. Data from 49 patients were finally analysed. Among these, 15 patients were treated with hyperthermic intraperitoneal chemotherapy. INTERVENTION: Each patient had a ZHF sensor placed on the skin surface of the forehead (TempZHF) and an oesophageal probe (TempEso) used as a reference method. Twenty-two patients also had a thermodilution arterial catheter (TempArt) placed in the axillary artery. MAIN OUTCOME MEASURES: Core temperature was continuously recorded from the three devices after induction of anaesthesia. Comparison of temperature measurements between methods was made using the Bland and Altman method during two separate periods according to the speed of core temperature changes. RESULTS: Compared with TempEso, bias and limits of agreement for TempZHF were 0.1 ±â€Š0.5 °C during slow core temperature changes periods and 0.6 ±â€Š1.8 °C during RCTC periods (P = 0.0002). Compared with TempArt, these values were -0.1 ±â€Š0.4 and 0.5 ±â€Š1.7 °C, respectively (P = 0.0039). The ZHF sensor was well tolerated. CONCLUSION: A SpotOn sensor using the ZHF method seems reliable for core temperature monitoring during abdominal surgery when variations in core temperature are slow rather than rapid. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02869828.

Postoperative fasting after general anaesthesia: A survey of French anaesthesiology practices.

BACKGROUND: Preoperative fasting is well codified worldwide. In contrast, the literature on the postoperative fasting (POF) is scarce, leading to potentially wide discrepancies among anaesthesiology practices. This survey assessed French POF practices. METHODS: From March 2013 to January 2014, a survey was conducted among anaesthesiologists, members of the French Society of Anaesthesiology and Intensive Care Medicine (SFAR). The POF durations of either fluid or solid food intake was assessed according to airway management procedures (endotracheal intubation [EI] or laryngeal mask [LMA]) and age of the patients (adult or paediatric). RESULTS: Seven hundred and fifty-four surveys were returned (67% from public hospital practitioners and 33% from private hospital and clinic practitioners). The majority of anaesthesiologists allowed fluid intake 2h after EI and immediately after discharge from PACU following LMA. For solid food resumption, it was 2h for children and 4h for adults after EI and 2h for both children and adults after LMA. Regardless of the airway management procedures, fasting was permitted immediately after PACU discharge more frequently in public than in private hospitals (36% vs. 33%, P<0.05). Four hours after the end of surgery, the rate was significantly higher in private than in public hospitals (93% vs. 89 %, P<0.001). CONCLUSIONS: All in all, POF lasted less than 4hours after surgery regardless of airway management. They were shorter with regard to fluid intake, paediatric patients and LMA in comparison with solid food, adult patients and EI respectively.

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units.

OBJECTIVE: The aims are to identify critical parameters influencing the drug mass flow rate of infusion delivery to patients during multidrug infusion and to discuss their clinical relevance. DATA SOURCES: A review of literature was conducted in January 2016 using Medline, Google Scholar, ScienceDirect, Web of Science and Scopus online databases. DATA EXTRACTION: References relating to the accuracy of fluid delivery via gravity-flow intravenous (IV) infusion systems and positive displacement pumps, components of IV administration sets, causes of flow rate variability, potential complications due to flow rate variability, IV therapies especially at low flow rates and drug compatibilities were considered relevant. DATA SYNTHESIS: Several parameters impact the delivery of drugs and fluids by IV infusion. Among them are the components of infusion systems that particularly influence the flow rate of medications and fluids being delivered. By their conception, they may generate significant start-up delays and flow rate variability. Performing multidrug infusion requires taking into account two main points: the common dead volume of drugs delivered simultaneously with potential consequences on the accuracy and amount of drug delivery and the prevention of drug incompatibilities and their clinical effects. CONCLUSION: To prevent the potentially serious effects of flow rate variability on patients, clinicians should receive instruction on the fluid dynamics of an IV administration set and so be able to take steps to minimise flow rate changes during IV therapy.

Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics.

French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions.

Compatibility of medications during multi-infusion therapy: A controlled in vitro study on a multilumen infusion device.

OBJECTIVE: Drug incompatibilities can jeopardize the safety and effectiveness of intravenous drug therapies, especially in the field of anaesthesia and intensive care. Patients receive many drugs simultaneously through limited venous accesses. This study was designed to confirm the impact of a multilumen infusion device on the occurrence of known physical drug incompatibilities. STUDY DESIGN: In vitro laboratory work. METHODS: Two infusion devices were studied: a standard single-lumen set and a multilumen infusion access device (Edelvaiss Multiline-8, Doran International). Up to six drugs were infused simultaneously: three acidic solutions of midazolam, amiodarone and dobutamine, and three alkaline solutions of furosemide, pantoprazole and amoxicillin/clavulanate. Saline, Ringer' solution and 5% dextrose were used as hydration vehicles with an infusion rate initially set at 100 mL/h and with stepwise decreases of 10 mL/h until precipitation. Two methods were used to highlight physical drug compatibility according to the European Pharmacopoeia: visual inspection of the extension set and an obscured-light sub-visible particle count test of infusions. The lowest infusion rate value for vehicle infusion to satisfy the two tests in all trials is reported for each infusion device. RESULTS: The standard set did not satisfy the test in 82% of the assessed drug combinations. The Edelvaiss Multiline-8 was able to prevent the occurrence of drug incompatibilities in 49% of the drug combinations tested. This device is therefore advantageous, especially when simultaneously infusing two or four incompatible drugs. CONCLUSIONS: Infusion device characteristics have an impact on physical drug incompatibilities. Our results confirm that the Edelvaiss Multiline-8 device prevents physical drug incompatibilities under specified conditions.

Influence of vancomycin infusion methods on endothelial cell toxicity.

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity.

Reversal of a rocuronium-induced grade IV anaphylaxis via early injection of a large dose of sugammadex.

AIM: To report rapid recovery from grade IV rocuronium-induced anaphylaxis with a large dose of sugammadex administered early after the onset of symptoms. CLINICAL FEATURES: A 22-yr-old female without relevant medical history developed an anaphylactic reaction within three minutes of rocuronium injection at induction of anesthesia for a routine cholecystectomy. During the first six minutes, she was unresponsive to usual treatment and her condition evolved to a grade IV anaphylaxis reaction despite a cumulated dose of epinephrine 0.7 mg. Sugammadex 14 mg·kg(-1), injected six minutes after rocuronium, resulted in total resolution of all manifestations of anaphylaxis within three minutes. The patient was discharged from hospital the next day. Allergy investigations confirmed rocuronium as the cause of anaphylaxis. CONCLUSION: Very early administration of a large dose of sugammadex may be an effective treatment for rocuronium-induced anaphylaxis.

Metronidazole and hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury.

The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 µg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.

This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.

Microdialysis study of cefotaxime cerebral distribution in patients with acute brain injury.

Central nervous system (CNS) antibiotic distribution was described mainly from cerebrospinal fluid data, and only few data exist on brain extracellular fluid concentrations. The aim of this study was to describe brain distribution of cefotaxime (2 g/8 h) by microdialysis in patients with acute brain injury who were treated for a lung infection. Microdialysis probes were inserted into healthy brain tissue of five critical care patients. Plasma and unbound brain concentrations were determined at steady state by high-performance liquid chromatography. In vivo recoveries were determined individually using retrodialysis by drug. Noncompartmental and compartmental pharmacokinetic analyses were performed. Unbound cefotaxime brain concentrations were much lower than corresponding plasma concentrations, with a mean cefotaxime unbound brain-to-plasma area under the curve ratio equal to 26.1 ± 12.1%. This result was in accordance with the brain input-to-brain output clearances ratio (CL(in,brain)/CL(out,brain)). Unbound brain concentrations were then simulated at two dosing regimens (4 g every 6 h or 8 h), and the time over the MICs (T>MIC) was estimated for breakpoints of susceptible and resistant Streptococcus pneumoniae strains. T>MIC was higher than 90% of the dosing interval for both dosing regimens for susceptible strains and only for 4 g every 6 h for resistant ones. In conclusion, brain distribution of cefotaxime was well described by microdialysis in patients and was limited.

The impact of multilumen infusion devices on the occurrence of known physical drug incompatibility: a controlled in vitro study.

BACKGROUND: Drug incompatibility is a problem, especially when managing patients in intensive care units. We designed the present study to assess the impact of multilumen infusion access devices on the occurrence of known physical drug incompatibility through a controlled in vitro study. METHODS: Three infusion devices connected to a single-lumen catheter were studied: a standard set with 2-port manifold and 1-m extension set and 2 multilumen infusion access devices: a 3-lumen extension set and a 9-lumen extension set (Edelvaiss-Multiline™; Doran International, Toussieu, France). For the 9-lumen extension set, 3 infusion access combinations were studied. Furosemide, midazolam, and saline were infused simultaneously through 3 infusion devices. Three concentrations of furosemide were tested. The infusion rate of saline (carrier) was initially set at 100 mL/h and stepwise decreased by 10 mL/h until precipitate formation. Physical incompatibility was assessed by 2 tests: visual inspection and the subvisible particle count test according to the European Pharmacopeia. The lowest saline infusion rate to prevent visible precipitate and attain an acceptable particle count (i.e., to pass "the 2 tests") was reported for each infusion set. RESULTS: The standard set revealed visible precipitate even at the highest saline flow rate (100 mL/h). The 3-lumen device prevented drug precipitation using the 2 lowest furosemide concentrations with a saline infusion rate that decreased with furosemide concentration. The 9-lumen infusion access device prevented drug precipitation whatever the furosemide concentration for 2 access combinations using saline infusion rates of between 20 and 60 mL/h but not for a third access combination, despite saline infusion rates equal to 100 mL/h. CONCLUSIONS: Infusion device characteristics appear to have an impact on the physical compatibility of the 2 drugs. Under specified conditions, the 9-lumen infusion access device prevents physical furosemide-midazolam incompatibility.

Benefits of an early cooling phase in continuous renal replacement therapy for ICU patients.

BACKGROUND: Lowering the temperature setting in the heating device during continuous venovenous hemofiltration (CVVH) is an option. The purpose of this study was to determine the effects on body temperature and hemodynamic tolerance of two different temperature settings in the warming device in patients treated with CVVH. METHODS: Thirty patients (mean age: 66.5 years; mean SAPS 2: 55) were enrolled in a prospective crossover randomized study. After a baseline of 2 h at 38°C, the heating device was randomly set to 38°C (group A) and 36°C (group B) for 6 h. Then, the temperatures were switched to 36°C in group A and to 38°C in group B for another 6 h. Hemodynamic parameters and therapeutic interventions to control the hemodynamics were recorded. RESULTS: There was no significant change in body temperature in either group. During the first 6 h, group B patients showed significantly increased arterial pressure (p = 0.01) while the dosage of catecholamine was significantly decreased (p = 0.04). The number of patients who required fluid infusion or increase in catecholamine dosage was similar. During the second period of the study, hemodynamic parameters were unchanged in both groups. CONCLUSIONS: In patients undergoing CVVH, warming of the substitute over 36°C had no impact on body temperature. We showed that setting the fluid temperature at 36°C for a period of time early in the procedure is beneficial in terms of increased mean arterial pressure and decreased catecholamine infusion dosage.

Impact of physical incompatibility on drug mass flow rates: example of furosemide-midazolam incompatibility.

BACKGROUND: Patients in intensive care units receive many drugs simultaneously but through limited venous accesses. Several intravenous therapies have to be administered through the same catheter, thus increasing the risk of physicochemical incompatibility. The purpose of this work was to assess and to quantify the impact of physical incompatibility on the mass flow rates of drugs infused simultaneously to the patient, through an in vitro study. METHODS: Furosemide-midazolam incompatibility was used to assess the impact of physical incompatibility on drug mass flow rates. Furosemide, midazolam, and saline were simultaneously infused. A filter was added at the end of the infusion line to retain visible particles. Two infusion conditions were tested with and without visible particles. A partial least square method on UV spectra was used to determine simultaneously the concentrations of the two drugs at the egress of the terminal extension line. The drug mass flow rate (expressed as mg/h) was calculated as the product of drug concentration versus total flow rate. Observed/theoretical mass flow rate ratios for each drug (%) were determined per infusion condition. RESULTS: Even in the absence of visible particles, precipitation of furosemide led to a drug loss estimated at between 10% and 15%. Furosemide is more impacted by interaction because the pH of the mixture is acid and this form is poorly soluble in an aqueous solution. CONCLUSIONS: Physical incompatibility between furosemide and midazolam leads to a significant reduction in drug delivered to the patient and may result in treatment failure.