Development and Preliminary Validation of LoAD Calc, a Mobile App for Calculating the Maximum Safe Single Dose of Local Anesthetics.

Local anesthetics systemic toxicity can lead to life-threatening situations. Correct calculation of the maximum safe dose is therefore paramount in preventing such complications. Different solutions have already emerged to support anesthesiologists but are seldom used in clinical practice as they require either access to a computer or specific documents to be at hand. A mobile app could provide an easy and practical solution; however, the few apps already created for this purpose often lack key elements, allowing invalid data to be entered and suggesting doses that might exceed the maximum safe dose. We describe the development of LoAD Calc, a mobile health (mHealth) app developed using a modified version of the Information Systems Research framework, which adds design thinking modes to the original framework. The app was enhanced through multiple iterations and developed with the aid of contextual observations and interviews, brainswarming sessions, prototyping, and continuous feedback. The design process led to the creation of two prototypes which underwent thorough testing by a sample of eight anesthesiologists. The final version of the app, LoAD Calc, was deployed on Apple and Android mobile test platforms and tested again by the same sample until deemed fit for release.

The international ENIGMA-II substudy on postoperative cognitive disorders (ISEP).

There is a large controversy as to whether nitrous oxide (N2O) added to the anaesthetic gas mixture is harmful or harmless for postoperative cognitive function recovery. We performed a nested study in the ENIGMA-II trial and compared postoperative neurocognitive recovery of patients randomly receiving N2O (70%) or Air (70%) in 30% O2 during anesthesia. We included adults having non cardiac surgery. We compared recovery scores for episodic memory, decision making/processing speed and executive functions measured with the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB). Assessments were performed at baseline, seven and ninety days. At first interim analysis, following recruitment of 140 participants, the trial was suspended. We found that the mean (95%CI) changes of scores for episodic memory were in the Pocock futility boundaries. Decision making/processing speed did not differ either between groups (P > 0.182). But for executive functions at seven days, the mean number (95% CI) of problems successfully solved and the number of correct box choices made was higher in the N2O group, P = 0.029. N2O with the limitations of an interim analysis appears to have no harmful effect on cognitive functions (memory/processing speed). It may improve the early recovery process of executive functions. This preliminary finding warrants further investigations.

Learning process of ultrasound-guided Ilio-fascial compartment block on a simulator: a feasibility study.

BACKGROUND: Ultrasound-guided fascia iliaca compartment block (US-FICB) is not part of the learning curriculum of the emergency physicians (EP) and is usually performed by anesthesiologists. However, several studies promote EP to use this procedure. The goal of this study was to assess the feasibility of a training concept for non-anesthesiologists for the US-FICB on a simulator based on a validating learning path. METHOD: This was a feasibility study. Emergency physicians and medical students received a 1-day training with a learning phase (theoretical and practical skills), followed by an assessment phase. The primary outcome at the assessment phase was the number of attempts before successfully completing the procedure. The secondary outcomes were the success rate at first attempt, the length of procedure (LOP), and the stability of the probe, corresponding to the visualization of the needle tip (and its tracking) throughout the procedure, evaluated on a Likert scale. RESULTS: A total of 25 participants were included. The median number of attempts was 2.0 for emergency physicians and 2.5 for medical students, and this difference was not significant (p = 0.140). Seven participants (28%) succeeded at the first attempt of the procedure; the difference between emergency physicians and medical students was not significant (37% versus 21%; p = 0.409). The average LOP was 19.7 min with a significant difference between emergency physicians and medical students (p = 0.001). There was no significant difference regarding the stability of the probe between the two groups. CONCLUSION: Our 1-day training for non-anesthesiologists with or without previous skills in ultrasound seems to be feasible for learning the US-FICB procedure on a simulator.

Perioperative intravenous low-dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo-controlled study.

BACKGROUND: Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12 months after major lower back surgery. METHODS: In this single-centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg kg-1  hr-1 intraoperatively, and 0.1 mg kg-1  hr-1 from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo. RESULTS: Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4-106.7) and the median plasma level was 97 ng/ml (IQR 77.9-128.0). At 6 months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI -10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI -6.7 to 23.6; p = .319). CONCLUSIONS: In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low-dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12 months postoperatively. SIGNIFICANCE: We were unable to show any analgesic benefit of a short-term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged. PRIOR PRESENTATIONS: Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland. CLINICAL TRIAL NUMBER AND REGISTRY URL: Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).

Viral Sequences Detection by High-Throughput Sequencing in Cerebrospinal Fluid of Individuals with and without Central Nervous System Disease.

: Meningitis, encephalitis, and myelitis are various forms of acute central nervous system (CNS) inflammation, which can coexist and lead to serious sequelae. Known aetiologies include infections and immune-mediated processes. Despite advances in clinical microbiology over the past decades, the cause of acute CNS inflammation remains unknown in approximately 50% of cases. High-throughput sequencing was performed to search for viral sequences in cerebrospinal fluid (CSF) samples collected from 26 patients considered to have acute CNS inflammation of unknown origin, and 10 patients with defined causes of CNS diseases. In order to better grasp the clinical significance of viral sequence data obtained in CSF, 30 patients without CNS disease who had a lumbar puncture performed during elective spinal anaesthesia were also analysed. One case of human astrovirus (HAstV)-MLB2-related meningitis and disseminated infection was identified. No other viral sequences that can easily be linked to CNS inflammation were detected. Viral sequences obtained in all patient groups are discussed. While some of them reflect harmless viral infections, others result from reagent or sample contamination, as well as index hopping. Altogether, this study highlights the potential of high-throughput sequencing in identifying previously unknown viral neuropathogens, as well as the interpretation issues related to its application in clinical microbiology.

Ultrasound-guided continuous femoral nerve block: a randomized trial on the influence of femoral nerve catheter orifice configuration (six-hole versus end-hole) on post-operative analgesia after total knee arthroplasty.

BACKGROUND: Multiorifice catheters have been shown to provide superior analgesia and significantly reduce local anesthetic consumption compared with end-hole catheters in epidural studies. This prospective, blinded, randomized study tested the hypothesis that, in continuous femoral nerve block (CFNB) under ultrasound guidance, multiorifice catheter would reduce local anesthetic consumption at 24 h compared with end-hole catheter. METHODS: Eighty adult patients (aged ≥18 years) scheduled to undergo primary total knee arthroplasty under a combination of CFNB, sciatic nerve block and general anesthesia were randomized to CFNB using either a 3-pair micro-hole (Contiplex, BRAUN®, 20G - 400 mm) or an end-hole (Silverstim VYGON®, 20G - 500 mm) catheter. Once the femoral catheter was sited, a bolus of 20 mL lidocaine 1% was injected. An electronic pump then delivered an automated 5 mL bolus of ropivacaine 0.2% hourly, with 10 mL self-administered patient controlled analgesia boluses. RESULTS: There was no inter-group difference in either median number of ropivacaine boluses on demand during the first 24 h (4(2-7) vs. 4(2-8) in six-hole and end-hole groups, respectively; P = 0.832) or median ropivacaine consumption at 48 h (365(295-418) vs. 387(323-466); P = 0.452). No significant differences were recorded between the groups at 24 h regarding median average verbal rate pain scale (2(0-3) vs. 2(0-4); P = 0.486) or morphine consumption (0(0-20) vs. 0(0-20); P = 0.749). Quadriceps muscle strength declined to 7% (0-20) and 10% (0-28) in the six-hole and end-hole groups, respectively, at 24 h after surgery (P = 0.733). CONCLUSIONS: In this superiority trial, catheter orifice configuration did not influence the effectiveness of CFNB in this setting: quality of analgesia was similar, with no reduction in either local anesthetic or morphine consumption, and equivalent postoperative quadriceps weakness. TRIAL REGISTRATION: Retrospectively registered at ( NCT03376178 ). Date: 21 November 2017.

Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

BACKGROUND: Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. METHODS: One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. RESULTS: There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. CONCLUSIONS: In continuous interscalene blockade under ultrasound guidance after shoulder surgery, automated boluses of local anesthetic combined with PRN boluses did not provide any reduction in local anesthetic consumption or rescue analgesia, compared with continuous infusion combined with PRN boluses.

Cervical abscess complicating an ultrasound-guided interscalene catheter.

Perineural catheters are the technique of choice for postoperative analgesia after painful orthopedic surgery. Infectious complications associated with perineural catheters, although rare, are associated with increased morbidity and mortality, medical cost, and hospital length of stay. In this report, we describe a patient in whom a cervical abscess occurred after insertion of an ultrasound-guided interscalene catheter.

Perineural clonidine does not prolong levobupivacaine 0.5% after sciatic nerve block using the Labat approach in foot and ankle surgery.

BACKGROUND: There is controversy about the effectiveness of perineural clonidine used as an adjuvant to local anesthetics. This study investigated whether the addition of 150 µg clonidine to 0.5% levobupivacaine used for posterior sciatic nerve block would prolong the duration of analgesia. METHODS: This double-blind, prospective trial compared the analgesic characteristics of 20 mL plain levobupivacaine versus 20 mL levobupivacaine 0.5% plus 150 µg clonidine in a posterior sciatic nerve block (Labat approach) for foot and ankle surgery. Sixty patients were randomized and allocated to receive either levobupivacaine alone or levobupivacaine plus clonidine, to find a 30% prolongation of analgesia with the adjuvant, using the same SD. The onset and duration of the block (time from completion of block administration to first morphine request), the hemodynamic changes during surgery, the need for rescue analgesia, and technical or neurologic complications were assessed over a 24-hour period. RESULTS: The onset of sensory block (in minutes) was similar in the levobupivacaine and levobupivacaine plus clonidine groups (10 [5-20] vs 10 [5-23] minutes, median [interquartile range], respectively), as was the time to first request of pain medication (1215 [920-1530] vs 1275 [1067-1360] minutes, respectively). However, during surgery, statistically significantly more subjects in the levobupivacaine plus clonidine group than the levobupivacaine group experienced a decrease of more than 20% in systolic arterial pressure (50% vs 28% of patients, respectively; P < 0.028). No complications were noted in either group over 24 hours. CONCLUSIONS: Addition of 150 µg clonidine to 20 mL of levobupivacaine 0.5% in posterior gluteal (Labat) sciatic nerve block did not prolong the duration of analgesia but had a slight effect on systolic arterial pressure.

Levobupivacaine 0.5% provides longer analgesia after sciatic nerve block using the Labat approach than the same dose of ropivacaine in foot and ankle surgery.

BACKGROUND: Levobupivacaine and ropivacaine are 2 left enantiomeric molecules frequently used for peripheral nerve blocks because of their safe clinical profile. Levobupivacaine is more lipophilic and theoretically more potent than ropivacaine, but clinical studies show conflicting results in terms of anesthetic and analgesic characteristics. We hypothesized that the pure S-enantiomer of bupivacaine provides longer-lasting analgesia than ropivacaine. METHODS: We compared the analgesic characteristics of 20 mL levobupivacaine versus 20 mL ropivacaine 0.5% in a posterior sciatic nerve block (Labat approach) for foot and ankle surgery. In a double-blind, randomized, prospective design, 80 patients received either substance. We assessed the onset, duration, and success of the block, and the need for rescue analgesia and technical or neurologic complications over 24 hours. RESULTS: The onset of sensory block (minutes) and the success rate were similar in levobupivacaine and ropivacaine groups (onset, 15 minutes [5-40 minutes] vs 15 minutes [5-60 minutes], respectively; success rate, 90% vs 92.5%). The average time for the first request of pain medication provided by 20 mL levobupivacaine 0.5% was significantly longer than with ropivacaine (1605 minutes [575-2400 minutes] vs 1035 minutes [590-1500 minutes], P < 0.001). The need for postoperative rescue analgesia was higher in the ropivacaine group (37 of 40 [92.5%] vs 30 of 40 [75%], P < 0.034). No complications were noted in either group at 24 hours. CONCLUSION: Twenty milliliters levobupivacaine 0.5% in posterior gluteal (Labat) sciatic nerve block provided longer-lasting analgesia after foot and ankle surgery compared with the same dose of ropivacaine.

A new anatomical technique to investigate nerves by imagery.

INTRODUCTION: We describe a novel post mortem technique that makes it possible to visualise the nerve structure of the brachial plexus using imaging. MATERIALS AND METHODS: We dissected in situ the brachial plexus of a cadaver preserved by formaldehyde. A preparation composed of a mixture of baryte powder, water and colorant, was applied to all sides of the brachial plexus and blood vessels of the region under study. A high resolution CT scan was performed. With the aid of Mimics (Materialise) software, segmentation of all the nerve and vascular structures on each of the 650 slices obtained was performed. The Mimics software then compiled all the slices to generate a 3-dimensional STL image. RESULTS: The image obtained was printed with a stereolythography printer, to produce a plastic model representing part of the cervico-thoracic spinal cord, the ribs, sternum, scapula, humerus, and clavicle, with the left brachial plexus and the subclavian, axillary and brachial veins and arteries. CONCLUSIONS: This technique has the potential for a wide range of uses: for teaching anatomy, to improve teaching of medical techniques, 3-dimensional modelisation of other nerve structures. The advantage is that the model obtained is a faithful and realistic reproduction.

No differences between 20, 30, or 40 mL ropivacaine 0.5% in continuous lateral popliteal sciatic-nerve block.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the anesthetic and analgesic characteristics of the administration of an initial bolus of 20, 30, or 40 mL of ropivacaine 0.5% through a lateral popliteal sciatic catheter. METHODS: Sixty patients scheduled for foot surgery under continuous sciatic lateral popliteal nerve block were included in this double-blinded study. Patients were randomly assigned to 1 of 3 groups: 20 mL, 30 mL, or 40 mL of ropivacaine 0.5%. Time to obtain a complete sensory block and duration of analgesia were recorded. Failure of the continuous block and complications such as technical or neurologic problems were noted. RESULTS: Data are presented as mean +/- SD, median and ranges, or percent of patients and were compared by application of analysis of variance or Kruskal-Wallis when required. Time to complete sensory block (31 [10-70] v 25 [5-50] v 25 [5-40] min), percentage of failure (5% v 5% v 0%), and duration of action (995 [278-1,800] v 967 [420-2,175] v 915 [190-1,900] min) were not statistically different between 20 mL, 30 mL, and 40 mL ropivacaine 0.5% groups, respectively. No complications were noted. CONCLUSIONS: This dose-response study shows that 20 mL of ropivacaine 0.5% injected through an indwelling lateral popliteal catheter is the optimal dose for foot surgery. Higher doses of 30 mL or 40 mL did not provide any further advantage.

Intrathecal sufentanil is more potent than intravenous for postoperative analgesia after total-hip replacement.

BACKGROUND AND OBJECTIVES: In our clinical experience, sufentanil is more effective when administered intrathecally than intravenously. To test this hypothesis, we compared the analgesic characteristics of 7.5 microg of intrathecal or intravenous sufentanil for pain relief after total-hip replacement. METHODS: A randomized, double-blind study was conducted of 40 patients older than 75 years who experienced total-hip arthroplasty in which continuous spinal anesthesia was administered. In the recovery room, as soon as a pain score higher than 3 on a scale of 10 on a visual analog scale was reported, either 7.5 microg intrathecal or 7.5 microg intravenous sufentanil were given. If the pain score remained higher than 3 at 20 minutes after sufentanil administration,1.25 mg of "rescue" intrathecal bupivacaine were given. RESULTS: During the first 20 minutes after intrathecal or intravenous injection, a significantly faster relief of pain was observed for the intrathecal group from 2.5 until 20 minutes. Significantly, more patients needed rescue bupivacaine in the intravenous group (7 of 20 v 0 of 20, P < .008), whereas significantly more patients in the intrathecal group reached a pain score of 0 (20 of 20 v 9 of 20, P < .001). The time to the first analgesic intervention for a pain score greater than 3 was significantly longer in the intrathecal group (224 +/- 100 v 98 +/- 60 minutes, P < .001). Pruritus was observed only in 5 patients of the intrathecal group (P < .047), whereas peripheral oxygen saturation under 95% was observed only in 6 patients in the intravenous group (P < .045). CONCLUSIONS: After total-hip replacement, intrathecal route of sufentanil administration rapidly offers excellent analgesia of better quality and longer duration when compared with the intravenous route.

Duration of analgesia is similar when 15, 20, 25 and 30 mL of ropivacaine 0.5% are administered via a femoral catheter.

PURPOSE: This dose-response study was designed to determine the most appropriate dose of ropivacaine 0.5% injected via an indwelling femoral catheter for perioperative peripheral analgesia for total knee replacement (TKR). METHODS: 84 patients were allocated randomly to four groups and received, via a femoral catheter, either 15, 20, 25 or 30 mL of ropivacaine 0.5% in a double-blind fashion. An anterior sciatic block with 20 mL bupivacaine 0.5% was also performed. The evolution of sensory block of femoral, obturator and lateral femoral cutaneous nerves and motor block of femoral nerve were tested every five minutes during the first 30 min. The percentage of patients with complete sensory block of both femoral and obturator nerves determined success rate. General anesthesia was then induced. After surgery, patient-controlled analgesia (PCA) with ropivacaine 0.2% was available via the femoral catheter. The interval between the initial injection and the first PCA administration determined duration of action. RESULTS: The duration of action was not different between the four solutions tested i.e., 534 +/- 379 min for 15 mL, 799 +/- 364 min for 20 mL, 624 +/- 342 min for 25 mL and 644 +/- 266 min for 30 mL. The percentage of patients with complete sensory femoral and obturator blocks was, respectively, 60%, 95%, 85% and 70% for 15, 20, 25 and 30 mL (P = 0.008/15 mL vs 20 mL). CONCLUSION: Although there is no difference in duration of analgesia, because of better sensory spread, 20 mL of ropivacaine 0.5% appears to be the most appropriate dose for peripheral analgesia after TKR.

Cerebrospinal fluid tau and Abeta42 concentrations in healthy subjects: delineation of reference intervals and their limitations.

Many limitations and conflicting results have cast serious doubts on the validity of cerebrospinal fluid tau and Abeta42 levels for the biological diagnosis of Alzheimer's disease, particularly extreme variations of the reference limits found by unrelated groups as a consequence of different reference populations used. In this study, we addressed the issue of defining reference limits for cerebrospinal fluid tau and Abeta42 in healthy adult individuals. One hundred and five neurologically intact subjects were enrolled according to strict inclusion criteria, 10 of them with autopsy confirmation of brain integrity. All cerebrospinal fluid samples were similarly and optimally processed as were the dosage methods used and the statistical analyses performed. A robust correlation with age was demonstrated for Abeta42 but not for tau. For tau, we found that an upper cut-off value of 443 ng/l allowed 95% of the subjects to be correctly classified as normal. For Abeta42, a lower cut-off value of 90 ng/l allowed a correct classification of 90% of the subjects. However, a large variance of the reference values, partly explained by the potential contamination of the reference population with presymptomatic dementia patients, may limit the use of reference limits based on living subjects. We propose that the issue of defining reference limits for both cerebrospinal fluid tau and Abeta42 may ultimately be settled by studying large numbers of autopsy-proven neurologically intact individuals only.

Isobaric versus hypobaric spinal bupivacaine for total hip arthroplasty in the lateral position.

UNLABELLED: Total hip arthroplasty (THA) is frequently performed under spinal anesthesia using either isobaric or hypobaric anesthetic solution. However, these two solutions have never been compared under similar surgical conditions. In the present study, we compared the anesthetic and hemodynamic effects of isobaric and hypobaric bupivacaine in 40 ASA physical status I-II patients undergoing THA in the lateral decubitus position under spinal anesthesia. With operative side up, patients randomly received, in a double-blinded manner, a spinal injection of 3.5 mL (17.5 mg) of plain bupivacaine mixed with either 1.5 mL of normal saline (isobaric group) or 1.5 mL of distilled water (hypobaric group). Sensory level and degree of motor block were evaluated on the nondependent and dependent sides until regression to L2 and total motor recovery. Hemodynamic changes during the first 45 min after spinal injection, and the time between spinal administration and first analgesic for a pain score >3 (on a 0-10 scale) were noted. Demographic characteristics of both groups were comparable. Upper sensory level and maximal degree of motor block were comparable between the operative and nonoperative sides in each group and between corresponding sides in both groups. Compared with the isobaric group, in the hypobaric group there was a prolonged time to sensory regression to L2 on the operative side (287 +/- 51 versus 242 +/- 36 min, P < 0.004) and a prolonged time to first analgesic (290 +/- 46 versus 237 +/- 39 min, P < 0.001). No difference in quality of motor block was noted at the end of surgery. Hemodynamic changes were comparable. We conclude that for THA in the lateral position, spinal hypobaric bupivacaine seems to be superior to isobaric in that it prolongs the sensory block on the operative side and delays the use of analgesics after surgery without further compromising hemodynamic stability. IMPLICATIONS: For total hip arthroplasty in the lateral position, spinal hypobaric bupivacaine compared with isobaric prolonged sensory block at the operative side and delayed the time to first analgesic.

Cerebrospinal fluid density influences extent of plain bupivacaine spinal anesthesia.

BACKGROUND: The attempts to explain the unpredictability of extent of spinal block provided by plain local anesthetic solutions have resulted in many clinical reports; however, causes of this uncertainty are as yet unknown. Recently, normal values of the human cerebrospinal fluid densities have been studied showing important interindividual variations, especially between females and males. The current study was designed to evaluate as primary endpoint the influence of cerebrospinal fluid density values on the extent of spinal block with plain bupivacaine. The ancillary endpoints were search of factors explaining the interindividual differences in cerebrospinal fluid density values reported and determination of the relation between upper extent and regression of spinal anesthesia. METHODS: Sixty-four consecutive patients undergoing peripheral orthopedic surgery with spinal block were enrolled. Spinal anesthesia was performed in the lateral decubitus position with the operated side upward. Two milliliters of cerebrospinal fluid was sampled before injection of 3 ml plain bupivacaine 0.5%. The patient was immediately turned supine and remained in the horizontal position until the end of the study. Maximal sensory block level and time to sensory regression to L4 were determined for each patient enrolled. Cerebrospinal fluid and bupivacaine densities as well as cerebrospinal proteins, glucose, sodium, and chloride concentrations were measured. RESULTS: A highly significant correlation between cerebrospinal fluid density and maximal sensory block level was found (P = 0.0004). However, this correlation was poorly predictive (R(2) = 0.37). Cerebrospinal fluid density, proteins, and glucose concentrations were significantly higher in men than in women: 1.000567 +/- 0.000091 versus 1.000501 +/- 0.000109 g/ml (P = 0.014), 0.46 +/- 0.18 versus 0.32 +/- 0.13 g/l (P = 0.001), and 3.27 +/- 0.7 versus 2.93 +/- 0.5 mM (P = 0.023), respectively. A highly significant (P = 0.0004) and predictive (R(2) = 0.73) inverse correlation was found between maximal upper sensory extent and sensory regression to L4. CONCLUSION: These findings indicate an influence of cerebrospinal fluid density on subarachnoid distribution of 3 ml plain bupivacaine 0.5% and show that with higher cerebrospinal fluid densities, a higher spinal block level can be expected.