The Potential Neurological Impact of Intraoperative Hyponatremia Using Histidine-Tryptophan-Ketoglutarate Cardioplegia Infusion in Adult Cardiac Surgery.

Background and Objectives: The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods: A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results: The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group (p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 (p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions: HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.

Pharmacokinetics and Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery.

BACKGROUND: Intraperitoneal chloroprocaine has been used during cesarean delivery to supplement suboptimal neuraxial anesthesia for decades. The short in vitro half-life of chloroprocaine (11-21 seconds) has been cited to support the safety of this approach. However, there are no data regarding the rate of absorption, representing patient drug exposure, through this route of administration. Accordingly, we designed a study to determine the in vivo half-life of intraperitoneal chloroprocaine and assess clinical tolerability. METHODS: We designed a single-center, prospective, cohort, multiple-dose escalation study of women 18 to 50 years of age undergoing cesarean delivery with spinal anesthesia. Chloroprocaine (40 mL) was administered after delivery of the newborn and before uterine closure. The first cohort (n = 5) received 1%, the second cohort (n = 5) received 2%, and the third cohort (n = 5) received 3% chloroprocaine solution. Maternal blood samples were obtained before administration and 1, 5, 10, 20, and 30 minutes after dosing. The primary objective was to define the pharmacokinetic profile of intraperitoneal chloroprocaine, including in vivo half-life. The secondary objective was to evaluate tolerability through determination of peak plasma concentration and prospective assessment for local anesthetic systemic toxicity. RESULTS: The peak plasma concentration occurred 5 minutes after intraperitoneal administration in all 3 cohorts: 64.8 ng/mL (6.5 µg/kg), 28.7 ng/mL (2.9 µg/kg), and 799.2 ng/mL (79.9 µg/kg) for 1%, 2%, and 3% chloroprocaine, respectively. The in vivo half-life of chloroprocaine after intraperitoneal administration was estimated to be 5.3 minutes (95% confidence interval, 4.0-6.6). We did not detect clinical signs of local anesthetic systemic toxicity in any of the 3 cohorts. CONCLUSIONS: The in vivo half-life of intraperitoneal chloroprocaine (5.3 minutes) is more than an order of magnitude greater than the in vitro half-life (11-21 seconds). However, maximum plasma concentrations of chloroprocaine (C max range, 0.05-79.9 µg/kg) were not associated with local anesthetic systemic toxicity and remain well below our predefined safe level of exposure (970 µg/kg) and levels associated with clinical symptoms (2.6-2.9 mg/kg). Therefore, our study suggests that intraperitoneal chloroprocaine, in a dosage ≤1200 mg, administered after fetal extraction, is well tolerated during cesarean delivery.

ED 90 of Intrathecal Chloroprocaine With Fentanyl for Prophylactic Cervical Cerclage: A Sequential Allocation Biased-Coin Design.

BACKGROUND: Chloroprocaine is a short-acting local anesthetic that has been used for spinal anesthesia in outpatient surgery. There is limited experience with spinal chloroprocaine for prophylactic cervical cerclage placement. We sought to determine the effective dose of intrathecal chloroprocaine for 90% of patients (ED90) undergoing prophylactic cervical cerclage placement. We hypothesized that the ED90 of intrathecal chloroprocaine when combined with 10-ug fentanyl would be between 33 and 54 mg. METHODS: In this prospective 2-center double-blinded study, we enrolled women undergoing prophylactic cervical cerclage placement under combined spinal-epidural anesthesia. A predetermined dose of intrathecal 3% chloroprocaine with fentanyl 10 ug was administered. The initial dose was 45-mg intrathecal chloroprocaine. Subsequent dose adjustments were determined based on the response of the previous subject using an up-down sequential allocation with a biased-coin design. A dose was considered effective if at least a T12 block was achieved, and there was no requirement for epidural activation or intraoperative analgesic supplementation during the procedure. The primary outcome was the ED90 of intrathecal chloroprocaine with fentanyl 10 ug. Secondary outcomes included duration of surgery, anesthetic side effects, time to resolution of motor and sensory block, time to achieve recovery room discharge criteria, and patient satisfaction with anesthetic care. Isotonic regression was used to estimate the ED90. RESULTS: Forty-seven patients were enrolled into the study. Two patients were excluded (1 protocol violation and 1 failed block). In total, 45 patients completed the study. The estimated ED90 (95% confidence interval) for intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg (45.0-50.1 mg). The median (interquartile range [IQR]) duration of surgery was 15 (10-24) minutes. Resolution of the motor (Bromage 0) and sensory block took a median time of 60 (45-90) minutes and 90 (75-105) minutes, respectively. The median time to achieve recovery room discharge criteria was 150 (139-186) minutes. Satisfaction with anesthetic management was high in all patients. There were no reports of postdural puncture headache or transient neurological symptoms postoperatively. CONCLUSIONS: The ED90 of intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg. Intrathecal chloroprocaine was associated with rapid block recovery and high patient satisfaction, which makes it well suited for outpatient obstetric procedures.

Influence of height on ED95 of intrathecal 2-chloroprocaine for knee arthroscopy: A prospective dose-response clinical trial.

BACKGROUND: Plain 2-chloroprocaine , a rapid acting amino-ester-type local anaesthetic, is used in short ambulatory procedures under spinal anaesthesia. The ED 95 of 2-chloroprocaine for lower limb surgery has not yet been defined. Moreover, patients' body height could influence the effects of the administered dose. OBJECTIVES: The aim of this study was to determine the ED 95 of plain 2-chloroprocaine based on the height of patients undergoing ambulatory knee arthroscopy under spinal anaesthesia using the continual reassessment statistical method (CRM). DESIGN: Prospective, dose-response, double blind, controlled, bi-center, clinical trial. SETTING: One university teaching hospital in Brussels and one general teaching hospital, Braine l'Alleud, Belgium. Université libre de Bruxelles. PATIENTS: ASA I-III (120 patients) scheduled for day-case knee arthroscopy under spinal anaesthesia. INTERVENTIONS: Patients were divided into three groups of 40, each comprising 10 cohorts of 4 patients, according to their respective heights (Group 1: 150-165 cm, Group 2: 166-180 cm, Group 3: 181-195 cm). Each patient enrolled into one of the 3 groups received an intrathecal dose of plain 2-chloroprocaine determined by the CRM. The starting doses for the first cohorts of four were 40 mg in group 1, 45 mg in group 2 and 50 mg in group 3. The doses for subsequent cohorts were determined by CRM of outcomes in all patients in the previous competed cohorts. Anaesthesia was considered successful when there was a lack of pinprick or cold sensation up to T12, the visual analogue scale score for tourniquet pain was < 2 and no pain during surgery. MAIN OUTCOMES: The primary outcome was the success or failure of the block. Side effects were also recorded. RESULTS: ED 95 of 2-chloroprocaine is 40 mg in group 1, 35 mg in group 2, 45 mg in group 3. Groups were different in terms of height and gender ( P  < 0.05) and similar in terms of body mass index and age ( P  > 0.05). CONCLUSION: The ED95 of intrathecal 2-chloroprocaine for patients undergoing ambulatory knee arthroscopy is between 35 and 45 mg. Height could be a factor involved in the calculation, and patient sex could partly explain the nonlinear relation between height and dose. TRIAL REGISTRY NUMBER: Clinicaltrials.gov NCT03882489.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

Comparison of Chloroprocaine Versus Lidocaine With Epinephrine, Sodium Bicarbonate, and Fentanyl for Epidural Extension Anesthesia in Elective Cesarean Delivery: A Randomized, Triple-Blind, Noninferiority Study.

BACKGROUND: For emergent intrapartum cesarean delivery (CD), the literature does not support the use of any particular local anesthetic solution to extend epidural analgesia to cesarean anesthesia. We hypothesized that 3% chloroprocaine (CP) would be noninferior to a mixture of 2% lidocaine, 150 µg of epinephrine, 2 mL of 8.4% bicarbonate, and 100 µg of fentanyl (LEBF) in terms of onset time to surgical anesthesia. METHODS: In this single-center randomized noninferiority trial, adult healthy women undergoing CD were randomly assigned to epidural anesthesia with either CP or LEBF. Sensory blockade (pinprick) to T10 was established before operating room (OR) entry for elective CD. On arrival to the OR, participants received the epidural study medications in a standardized manner to simulate the conversion of "epidural labor analgesia to surgical anesthesia." The primary outcome was the time to loss of touch sensation at the T7 level. A noninferiority margin was set at 3 minutes. The secondary outcome was the need for intraoperative analgesia supplementation. RESULTS: In total, 70 women were enrolled in the study. The mean onset time to achieve a bilateral sensory block to touch at the T7 dermatome level was 655 (standard deviation [SD] = 258) seconds for group CP and 558 (269) seconds for group LEBF, a difference in means of 97 seconds (90% confidence interval [CI], SD = -10.6 to 204; P = .10 for noninferiority). The upper limit of the 90% CI for the mean difference exceeded the prespecified 3-minute noninferiority margin. There was no meaningful difference in the requirement for intraoperative analgesia between the 2 groups. CONCLUSION: Both anesthetic solutions have a rapid onset of anesthesia when used to extend low-dose epidural sensory block to surgical anesthesia. Data from the current study provide insufficient evidence to confirm that CP is noninferior to LEBF for rapid epidural extension anesthesia for CD, and further research is required to determine noninferiority.

The Effect of Cardiac Preservation Solutions on Heart Transplant Survival.

BACKGROUND: Limited data exist that compare the predominant cardiac preservation solutions (CPSs). MATERIALS AND METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 1, 2004 to March 31, 2018, for donor hearts. Of 34,614 potential donors, 21,908 remained after applying the exclusion criteria. The CPS analyzed included saline, the University of Wisconsin (UW), cardioplegia, Celsior, and Custodiol. The primary endpoints were recipient survival and posttransplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: Saline was used as the CPS in 2549 patients (12%), UW in 10,549 (48%), cardioplegia in 1307 (6%), Celsior in 5081 (23%), and Custodiol in 2422 (11%). Donor age ranged from 15 to 68 y (mean = 32.0 y, median = 30.0 y), and 71% were male. Adjusted survival probabilities of recipients whose donor hearts were procured with saline was 96% 30 d, 90% 1 y, UW: 97% 30 d, 92% 1 y, cardioplegia: 95% 30 d, 87% 1 y, Celsior: 96% 30 d, 90% 1 y, and Custodiol: 97% 30 d, 92% 1 y. When these comparisons were adjusted for donor age, sex, ethnicity, ischemic time, recipient age, sex, ethnicity, creatinine, ventricular assist device (VAD), length of stay, region and days on waiting list, cardioplegia solution was demonstrated to have a higher risk of death (30 d, 1 y, overall) and posttransplant rejection versus UW (odds ratio 1.70, P = 0.001; odds ratio 1.63, P < 0.001; hazard ratio 1.22, P < 0.001; hazard ratio 1.21, P < 0.001, respectively). CONCLUSIONS: Cardioplegia solutions for cardiac preservation are associated with a higher mortality in heart transplant recipients.

Impact of Crystalloid or Albumin Priming of the Heart-Lung Machine on Inhospital Outcome after Coronary Artery Bypass Surgery.

BACKGROUND: Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome. METHODS: We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters. RESULTS: There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the "Sepsis-3 Guidelines," the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable. CONCLUSION: The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery.

Bretschneider (Custodiol®) and St. Thomas 2 Cardioplegia Solution in Mitral Valve Repair via Anterolateral Right Thoracotomy: A Propensity-Modelled Comparison.

BACKGROUND: Single-dose cardioplegia is preferred in minimal invasive mitral valve surgery to maintain the adjustment of the operative site without change of preset visualization. The aim of our study was to compare two widely used crystalloid cardioplegias Bretschneider (Custodiol®) versus St. Thomas 2 in patients who underwent mitral valve repair via small anterolateral right thoracotomy. MATERIAL AND METHODS: From May 2012 until February 2019, 184 isolated mitral valve procedures for mitral valve repair via anterolateral right thoracotomy were performed using Bretschneider (Custodiol®) cardioplegia (n = 123) or St. Thomas (n = 61). Primary efficacy endpoint was peak postoperative high-sensitivity cardiac troponin (hs-cTnT) during hospitalization. Secondary endpoints were peak creatine kinase-muscle brain type (CK-MB) and creatine kinase (CK) as well as safety outcomes. We used inverse probability of treatment weighting (IPTW) in order to adjust for confounding by indication. RESULTS: Peak hs-cTnT was higher after use of Bretschneider (Custodiol®) (geometric mean 716 mg/L, 95% confidence interval (CI) 605-847 mg/L) vs. St. Thomas 2 (561 mg/L, CI 467-674 mg/L, p = 0.047). Peak CK-MB (geometric mean after Bretschneider (Custodiol®): 40 µg/L, CI 35-46, St. Thomas 2: 33 µg/L, CI 27-41, p = 0.295) and CK (geometric mean after Bretschneider (Custodiol®): 1370 U/L, CI 1222-1536, St. Thomas 2: 1152 U/L, CI 972-1366, p = 0.037) showed the same pattern. We did not see any difference with respect to postoperative complications between treatment groups after IPTW. CONCLUSION: Use of St. Thomas 2 cardioplegia was associated with lower postoperative peak levels of all cardiac markers that reflect cardiac ischemia such as hs-cTnT, CK, and CK-MB as compared to Bretschneider (Custodiol®) in propensity-weighted treatment groups.

[Evaluation of spinal anesthesia in urological outpatient surgery, comparison between two local anesthetics (Chloroprocaine/Bupivacaine)]. / Évaluation de la rachianesthésie en chirurgie ambulatoire urologique, comparaison entre deux anesthésiques locaux (Chloroprocaïne/Bupivacaïne).

INTRODUCTION: Spinal anesthesia in outpatient urology is controversial (longer hospital stay, risk of urinary retention). The main goal was to evaluate outpatient spinal anesthesia and to compare 2 local anesthetics secondarily. MATERIAL: Monocentric retrospective study including all patients undergoing surgery in urological ambulatory surgery under spinal anesthesia between December 2011 and May 2015, split into two groups according to the local anesthetic used: bupivacaine (BP) and chloroprocaine (CP). Quantitative variables were compared by Student's t-test, qualitative variables by χ2 test. RESULTS: Seventy-one (95%) out of the 75 patients included have been discharged the same day. Discharge was impossible in these cases: patient alone at home (1), bladder clot (1), JJ intolerance (1), delayed micturition (1). The mean duration of the procedure was 27±19min, the SSPI's was 55±31min, the stay's was 360±91min. A total of 45 patients (60%) received BP and 30 (40%) received CP. The mean residence time in SSPI was significantly reduced in the CP group (47±24min vs. 61±34min, P=0.04). One patient experienced urination delay in the BP group with no significant difference. No significant difference for the other criteria studied despite the mean age, which is higher in the CP group (P=0.02). CONCLUSION: Spinal anesthesia is adapted to ambulatory urology, and does not increase the risk of urinary retention, especially with CP that would decrease the length of stay in SSPI compared to BP. LEVEL OF EVIDENCE: 4.

Custodiol Solution and Cold Blood Cardioplegia in Arterial Switch Operation: Retrospective Analysis in a Single Center.

BACKGROUND: The cardioplegia is one of the most significant tools used to increase myocardial protection. The aim of our study is to compare the use of Custodiol solution versus intermitted blood cardioplegia in a retrospective analysis of data for patients who underwent arterial switch operation in our institution. MATERIAL AND METHODS: From January 2008 to March 2011, myocardial protection was performed in 44 neonates (blood group) with intermittent blood cardioplegia. From March 2011 to November 2014, myocardial protection was performed in 50 neonates (Custodiol group) with one-shot anterograde Custodiol cardioplegia. RESULTS: Cardiopulmonary bypass and aortic cross-clamp were more favorable in Custodiol group (p-value 0.005 and ≤ 0.00001). The rate of delayed sternal closure was 63.6% in the blood group and 52% in the Custodiol group (p = 0.25). In the postoperative outcomes we did not find differences between the two groups. The 30-day mortality was one patient in the blood group (p = 0.46). We observed a transient ischemic electrocardiogram in 10 patients of the blood group and in 14 of the Custodiol group (p = 0.72), all cases with full resolution during hospitalization without coronary reoperation. A trend of higher peak of troponin-I and brain natriuretic peptide in Custodiol group has been reported. CONCLUSION: No prefect cardioplegia exists, the Custodiol solution does not cause extra/additional myocardial damage in arterial switch operation. In our experience this strategy seems warranted to simplify the procedure and to be more comfortable for the surgeon.

Corneal thickness differences between sexes after oxybuprocaine eye drops.

PURPOSE: We aimed to analyze the corneal thickness (CT) values of female and male subjects before and after instillation of oxybuprocaine 0.4% anesthetic eye drops. METHODS: The CT of 30 female subjects and 28 male subjects was measured using scanning-slit corneal topography (Orbscan Topography System II, Orbscan, Inc, Salt Lake City, UT). Measurements were carried out before and 3 minutes after the instillation of oxybuprocaine 0.4% eye drops. RESULTS: The difference between the baseline values and those obtained after anesthesia ranged as follows: male subjects: central, -26 to +24 µm; superior, -24 to +23 µm; inferior, -19 to +20 µm; nasal, -25 to +30 µm; and temporal, -21 to +20 µm; female subjects: central, -16 to +24 µm; superior, -19 to +32 µm; inferior, -14 to +34 µm; nasal, -19 to +33 µm; and temporal, -36 to +16 µm. No significant differences were found in any corneal location in male subjects. The differences were significant at inferior (p = 0.001) and nasal (p = 0.011) corneal sites in female subjects. CONCLUSIONS: Oxybuprocaine anesthetic eye drops induce significant CT increases in female subjects but not in male subjects.

Comparison of renal perfusion solutions during thoracoabdominal aortic aneurysm repair.

BACKGROUND: To determine whether renal perfusion with cold crystalloid solution enriched with histidine-tryptophan-ketoglutarate (Custodiol; Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) provides better protection against renal ischemic injury than cold lactated Ringer's solution in patients undergoing thoracoabdominal aortic aneurysm open repair. METHODS: We analyzed a prospectively compiled database containing all 111 consecutive patients who underwent thoracoabdominal aortic aneurysm open repair at our center from 2008 to 2011. A cohort of 104 consecutive patients was identified of which 50 (48%) had renal perfusion with Custodiol and 54 (52%) with lactated Ringer's solution. Propensity score matching based on baseline clinical variables, which were expected to influence renal outcomes, was performed to correct for any bias that may have been associated with the use of Custodiol. Acute kidney injury (AKI) as defined by Kidney Disease Improving Global Outcomes guidelines and perioperative estimated glomerular filtration rate were compared in the two groups. Independent predictors of AKI were also identified by multivariate analysis. RESULTS: After propensity score matching, we were able to match 42 Custodiol cases one-to-one with those receiving perfusion with lactated Ringer's solution. Overall 30-day mortality was 5.9%; temporary hemodialysis or continuous veno-venous hemofiltration was needed in 4.8% of the patients without any case of dialysis at discharge. Freedom from AKI was significantly increased in the Custodiol group (38.1% vs 9.5%; P = .002) despite longer total renal ischemic time (51.5 ± 16.4 minutes vs 43.6 ± 16.0 minutes; P = .05). By analysis of variance for repeated measures, a significant upward trend of perioperative estimated glomerular filtration rate was observed in the Custodiol group (group × time interaction = F3,66; P < .001), and by multivariate analysis, Custodiol perfusion was the only independent predictor of non-AKI (P = .04). CONCLUSIONS: The use of Custodiol was safe and provided improved perioperative renal function compared with lactated Ringer's solution. Randomized trials are needed to confirm these data and to assess their clinical consequences.

Intrathecal 1% 2-chloroprocaine vs. 0.5% bupivacaine in ambulatory surgery: a prospective, observer-blinded, randomised, controlled trial.

BACKGROUND: This prospective, observer-blinded, randomised, multicentre study aimed at determining the non-inferiority of 50 mg of plain 1% 2-chloroprocaine vs. 10 mg of 0.5% plain bupivacaine in terms of sensory block onset time at T10 after spinal injection. The study hypothesis was that the difference in onset times of sensory block to T10 between the two drugs is ≤ 4 min. METHODS: One hundred and thirty patients undergoing lower abdominal or lower limb procedures (≤ 40 min) were randomised to receive one of two treatments: 50 mg of plain 1% 2-chloroprocaine (Group C, n = 66) or 10 mg of plain 0.5% bupivacaine (Group B, n = 64). Times to sensory and motor block onsets, maximum sensory block level, readiness for surgery, regression of sensory and motor blocks, first analgesic requirements, unassisted ambulation, home discharge, and side effects after 24 h and 7 days were registered blindly. RESULTS: Chloroprocaine was comparable with plain 0.5% bupivacaine in terms of time to sensory block at T10 level. Group C showed faster onsets of motor block (5 vs. 6 min), maximum sensory block level (8.5 vs. 14 min), resolution of sensory (105 vs. 225 min) and motor (100 vs. 210 min) blocks, unassisted ambulation (142.5 vs. 290.5 min), first analgesic requirement (120 vs. 293.5 min), and home discharge (150 vs. 325 min) (all comparisons, P < 0.05). No chloroprocaine patient developed transient neurological symptoms. CONCLUSION: Spinal anaesthesia with 50 mg of plain 1% 2-chloroprocaine is similar to 10 mg of plain 0.5% bupivacaine in terms of onset of sensory block at T10 but shows quicker recovery from anaesthesia than with 0.5% bupivacaine.

Local anaesthetics: 10 essentials.

This review seeks to address 10 essential questions regarding the clinical use of local anaesthetics. Each local anaesthetic has distinctive physicochemical properties but with the same mode of action; they block voltage-gated sodium channels in the axon. Sodium channel block is brought about by a conformational change and the creation of a positive charge in the channel pore. Different local anaesthetics can reach the local anaesthetic binding site in the axon from the cytoplasmic compartment (classic hydrophilic pathway), or directly via its lipid membrane (hydrophobic pathway), or can enter via large-pore channels (alternative hydrophilic pathway). Beyond the nervous system, local anaesthetics exert beneficial effects on pain and can affect the inflammatory response and the haemostatic system. There are problems with the efficacy of local anaesthetics in the presence of local inflammation, and with significant intravascular toxicity, which can be fatal. But when preventive measures are taken, the incidence of cardiac arrest is low. Intralipid has been proposed to treat systemic local anaesthetic overdose and has been enthusiastically adopted worldwide, even though the mechanism of action is incompletely understood. Intralipid is an aid to the management of local anaesthetic toxicity rather than an antidote and meticulous conduct of regional anaesthesia remains paramount. All local anaesthetics are toxic, in a dose- and time-dependent manner, on virtually all tissues, including nerves and muscles. The question of whether local anaesthetics protect against perioperative tumour progression cannot be answered at this moment, and results from clinical (retrospective) studies are equivocal. Future areas of interest will be the design of new subtype-specific sodium channel blockers, but as we look forward, older local anaesthetics such as 2-chloroprocaine are being reintroduced into the clinical setting. Multimodal perineural analgesia and liposomal bupivacaine may replace catheter techniques for some indications.

Comparison of Proparacaine, Tetracaine, and Oxybuprocaine in Corneal Sensitivity Measurement.

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.

Randomized trial of HTK versus warm blood cardioplegia for right ventricular protection in mitral surgery.

OBJECTIVES: To clarify the reliability of the one-shot histidine-tryptophane-ketoglutarate (HTK) cardioplegia for right ventricular (RV) myocardial protection during mitral surgery, in patients with or without pre-operative RV dysfunction. DESIGN: Sixty patients undergoing isolated mitral surgery were randomized to myocardial protection with either one-shot HTK or intermittent warm blood cardioplegia (WBC). The RV function was assessed by echocardiography and hemodynamic assessment. Pre-operative tricuspid annular plane systolic excursion (TAPSE), an index of RV systolic function was used to dichotomize groups into patients having impaired (TAPSE < 15) or preserved (TAPSE ≥ 15) RV function. RESULTS: There were no significant intergroup differences in the post-operative indexes of RV function in cases with TAPSE ≥ 15. In patients having TAPSE < 15 we observed statistically worse RV ejection fraction (RVEF, 15% ± 2% vs. 24% ± 3%), end-diastolic volume (RVEDV, 188 mL ± 20 vs. 179 mL ± 14) and fractional area change (RVFAC, 21% ± 6% vs. 30% ± 3%) after use of the HTK solution versus patients who received the WBC. These differences were associated with longer mechanical ventilation and ICU times in patients with impaired RV function and receiving HTK cardioplegia. In a substudy ten patients with TAPSE < 15 received intra-operative topical myocardial cooling in addition to HTK. The addition of topical cooling to HTK cardioplegia yielded statistically significant amelioration in post-operative RV function compared with patients who received the HTK solution without topical cooling (RVEF: 23% ± 3% vs. 15% ± 2%; RVEDV: 180 mL ± 9 vs. 188 mL ± 18; RVFAC: 8.5% ± 1% vs. 6% ± 2%). CONCLUSIONS: The one shot HTK solution offers inferior RV protection compared with WBC, mainly in patients with depressed pre-operative RV function. When adopting HTK cardioplegia the addition of topical cooling is strongly advised.

The use of 2-chloroprocaine for spinal anaesthesia.

Spinal anaesthesia is a safe and reliable anaesthetic modality for surgical procedures on the lower part of the body. However, because of the description of transient neurologic symptoms (TNS), most practitioners have abandoned intrathecal lidocaine. Chloroprocaine (2-chloroprocaine, CP) has been one candidate to replace lidocaine for short procedures, despite the fact that neurologic sequelae have been described following the intrathecal injection of large doses of preservative-containing CP intended for epidural use. The National Library of Medicine's Medline and the EMBASE databases were searched for the time period 1966 to April 2012. Fourteen studies of the use of intrathecal CP were analysed, including seven volunteer and seven clinical studies. Preservative-free CP appears to be a reliable local anaesthetic for short procedures. The duration of the surgical block can be adjusted by varying the dose between 30 and 60 mg. Two double-blind randomised controlled studies demonstrate decreased time to ambulation and discharge when CP is used for spinal anaesthesia when compared with other local anaesthetics. The addition of fentanyl appears to prolong the surgical block without significantly prolonging the time to discharge. There have been five possible cases of TNS following CP spinal anaesthesia in over 4000 patients, and a regressive incomplete cauda equina syndrome has been described. The short duration of spinal CP makes it a strong contender for outpatient anaesthesia. It appears to have a lower risk of TNS than lidocaine.