A randomized comparative evaluation of local infiltration analgesia, extended nerve blocks, and conventional analgesia in pain management after total knee arthroplasty.

OBJECTIVES: The aim of this study was to analyze the postoperative effects of extended nerve blocks and local infiltration analgesia (LIA) on postoperative pain control, muscle weakness, and blood loss after total knee arthroplasty (TKA). PATIENTS AND METHODS: Between February 24th 2020 and July 10th 2020, a total of 161 patients (55 males, 106 females; median age: 69.0 years [IQR 63.0-75.0], range, 41 to 81 years) who underwent primary TKA were randomly allocated into three parallel groups according to their concomitant procedure in a double-blind fashion: (i) those to whom nerve blockade was performed after competition of surgery under the duration of spinal anesthesia (n=50); (ii) those to whom LIA was performed during surgery (n=52), and (iii) control group (n=59). The content of LIA was 10-10 mL of 20 mg lidocaine with 0.01 mg adrenalin and 100 mg ropivacaine, 1 mL (30 mg) ketorolac, and 5 mL (500 mg) tranexamic acid was diluted by 50 mL 0.9% NaCl under aseptic conditions. Outcome parameters were the evaluation of pain until the evening of first postoperative day (24 to 36 h), mobilization, and blood loss within the first three postoperative days. RESULTS: The pain was maximal between 4 and 8 h postoperatively, when the effect of the spinal anesthetic drugs disappeared. During this critical period, tolerable pain (Numerical Rating Scale, NRS ≤3) was observed in 52%, 42%, and 19% of nerve blockade in LIA and control groups, respectively. None of the patients complained of high-intensity pain (NRS >8) in the LIA group, which was a significant difference from the block and control groups (10% and 14%, p<0.008, respectively). There was no significant muscle weakness associated with the use of this extended block. The decrease in hemoglobin level was significantly lower in the LIA group than in the control and block groups (odds ratio [OR]: 0.379, 95% confidence interval [CI]: 0.165-0.874 for nerve blockade vs. LIA, OR: 1.189, 95% CI: 0.491-2.880 for nerve blockade vs. control, OR: 0.319, 95% CI: 0.140-0.727, respectively). The common language effect size for pain in each referred interval in each group and for decrease of hemoglobin between the first and third postoperative days fell between 0.507 and 0.680. CONCLUSION: This study demonstrates that LIA technique offers a fast and safe treatment option for pain relief after TKA. No clinically relevant muscle weakness was observed among groups according to field block applications. Significant advantages were also achieved in blood loss.

Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study.

Background Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure-raising hormone aldosterone. Besides its well-described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors-independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium-stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo-controlled double-blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure-monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P=0.0002) and aldosterone (median [interquartile range], 440 [336-521] versus 237 [173-386] pmol/L; P<0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII-stimulated aldosterone secretion (P=0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. Conclusions Increased potassium intake potentiates AngII-stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013-004460-66; URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02380157.

First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose.

INTRODUCTION: While emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population. METHODS: From a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression. RESULTS: Fifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01-0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1-608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2-3.1). CONCLUSIONS: In ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.

The use of vasopressors during acute burn resuscitation.

BACKGROUND: Vasopressors may be required during acute burn resuscitation to support mean arterial blood pressure, but their use is not well-described in the burn literature. The purpose of this study was to examine vasopressor use during acute fluid resuscitation. METHODS: Retrospective review of adults with burns ≥ 20% TBSA admitted to an ABA-verified regional burn center. Patients administered an infusion of a vasopressor for at least 30 min during the 1 st 48 h post-burn formed the PRESSOR group while patients who did not receive vasopressors formed the NoPRESSOR group. RESULTS: We studied 52 burned adults, 85% of which had flame burns. Vasopressors were administered during resuscitation to 31% of patients. Vasopressor infusions began at 20.9 ± 10.9 h post burn and were continued for 16.8 ± 10.8 h. PRESSOR patients (N = 16) had significantly greater total (p = 0.001) and full thickness burn size (p < 0.001), and need for mechanical ventilation (p = 0.005) than NoPRESSOR patients (N = 36). PRESSOR and NoPRESSOR patients did not differ significantly in per cent predicted fluid volume received in the first 24 h (143 ± 58 Vs. 125 ± 46 respectively). PRESSOR patients compared to NoPRESSOR patients tended to have been administered 5% albumin (Alb) less often (38% Vs 47%) and high dose vitamin C (HDVC) more often during resuscitation (69% vs 17%). Multivariate regression analysis found that patient age (OR 1.189, 95% CI: 1.047, 1.351) and HDVC (OR 24.701, 95% CI: 1.558, 391.551) were independently associated with greater use of vasopressors. An inverse probability weighted propensity analysis also identified a significant association between HDVC and increased use of vasopressors (OR 6.902, 95 % CI: 2.503, 19.026), and significantly decreased vasopressor administration following Alb administration (OR 0.310, 95% CI: 0.130, 0.739). CONCLUSION: Advanced age appears to be the most important determinant of vasopressor use during resuscitation. While vasopressor requirements appear to have been increased by HDVC and decreased by Alb, this needs to be formally evaluated in a large randomized study.

Maintaining Access to Orthopaedic Surgery During Periods of Operating Room Resource Constraint: Expanded Use of Wide-Awake Surgery During the COVID-19 Pandemic.

INTRODUCTION: Wide-awake local anesthesia no tourniquet (WALANT) presents a nonstandard anesthetic approach initially described for use in hand surgery that has gained interest and utilization across a variety of orthopaedic procedures. In response to operating room resource constraints imposed by the COVID-19 pandemic, our orthopaedic service rapidly adopted and expanded its use of WALANT. METHODS: A retrospective review of 16 consecutive cases performed by 7 surgeons was conducted. Patient demographics, surgical details, and perioperative outcomes were assessed. The primary end point was WALANT failure, defined as intraoperative conversion to general anesthesia. RESULTS: No instances of WALANT failure requiring conversion to general anesthesia occurred. In recovery, one patient (6%) required narcotics for pain control, and the average postoperative pain numeric rating scale was 0.6. The maximum pain score experienced was 4 in the patient requiring postoperative narcotics. The average time in recovery was 42 minutes and ranged from 8 to 118 minutes. CONCLUSION: The WALANT technique was safely and effectively used in 16 cases across multiple orthopaedic subspecialties, including three procedures not previously described in the literature. WALANT techniques hold promise for use in future disaster scenarios and should be evaluated for potential incorporation into routine orthopaedic surgical care.

Increase in early wound leakage in total knee arthroplasty with local infiltrative analgesia (LIA) that includes epinephrine: a retrospective cohort study.

Background and purpose - After introducing a new local infiltration anesthesia (LIA) protocol with addition of 30 mL ropivacaine 2% and 1 mg epinephrine, we noted an increase in early wound leakage. As wound leakage is associated with prosthetic joint infection, our department aims to minimize postoperative wound leakage. This study evaluates the incidence of early wound leakage and postoperative pain after knee arthroplasty (KA) following adjustment of the LIA protocol with addition of 30 cc ropivacaine 2% and 1 mg epinephrine. Patients and methods - In this retrospective medical dossier study all patients (n = 502) undergoing a primary total or unicondylar knee arthroplasty between January 1, 2018 and July 1, 2019 were included. Patients received an LIA protocol containing 120 mL 2 mg/mL ropivacaine (ROPI- group; n = 256). After October 30, patients received an LIA protocol containing 150 mL 2 mg/mL ropivacaine with 1 mg epinephrine in the first 100 mL (ROPI + group; n = 246). The primary outcome measure was early wound leakage (< 72 hours postoperatively), defined as wound fluid leaking past the barrier of the wound dressing. Secondary outcome measure, 10-point numeric rating scale (NRS) pain (< 72 hours postoperatively) was also assessed. Data was evaluated using logistic regression. Results - The incidence of wound leakage was higher in the ROPI + group: 24% versus 17% in the ROPI- group (p = 0.06). After adjusting for the differences between surgeons the relative risk of this increase was 1.4 (1.0-2.0). The ROPI + and ROPI- group were similar regarding postoperative pain assessment. Interpretation - Adjustment of the LIA protocol with 30 mL 2% ropivacaine and 1 mg epinephrine led to an increase in early wound leakage in knee arthroplasty but no difference in pain scores.

Plating of clavicle fracture using the wide-awake technique.

BACKGROUND: Fixation of clavicle fractures has now become a more popular option as it provides better outcome compared with conservative management. Wide-awake local anesthesia no tourniquet (WALANT) has been effectively used in plating of distal radius and olecranon fractures. This paper expands the usage of WALANT into the shoulder girdle, namely plating of the clavicle that has not been described. The operation is typically performed under general anesthesia. METHODS: We report a case series of 16 patients who successfully underwent fixation of the clavicle under the wide-awake technique. The clavicle fractures were grouped under the AO Fracture Classification. The WALANT solution comprised 1% lidocaine, 1:100,000 epinephrine, and 10:1 sodium bicarbonate. A total of 40 mL was injected in each patient with 10 mL subcutaneously along the clavicle followed by 30 mL subperiosteally at multiple intervals and directions. RESULTS: The Numerical Pain Rating Score was 0 during WALANT injection and during surgery except for 2 patients with Numerical Pain Rating Scores of 1 and 2, respectively, during reduction. CONCLUSION: We conclude that clavicle plating under WALANT is a good alternative option of anesthesia.

Buffered lidocaine 1%/epinephrine 1:100,000 with sodium bicarbonate (sodium hydrogen carbonate) in a 3:1 ratio is less painful than a 9:1 ratio: A double-blind, randomized, placebo-controlled, crossover trial.

BACKGROUND: Neutralizing (buffering) lidocaine 1%/epinephrine 1:100,000 solution (Lido/Epi) with sodium hydrogen carbonate (NaHCO3) (also called sodium bicarbonate) is widely used to reduce burning sensations during infiltration of Lido/Epi. Optimal mixing ratios have not been systematically investigated. OBJECTIVES: To determine whether a Lido/Epi:NaHCO3 mixing ratio of 3:1 (investigational medicinal product 1) causes less pain during infiltration than a mixing ratio of 9:1 (IMP2) or unbuffered Lido/Epi (IMP3). METHODS: Double-blind, randomized, placebo-controlled, crossover trial (n = 2 × 24) with 4 investigational medicinal products (IMP1-4). RESULTS: The 3:1 mixing ratio was significantly less painful than the 9:1 ratio (P = .044). Unbuffered Lido/Epi was more painful than the buffered Lido/Epi (P = .001 vs IMP1; P = .033 vs IMP2). IMP4 (NaCl 0.9% [placebo]) was more painful than any of the anesthetic solutions (P = .001 vs IMP1; P = .001 vs IMP2; P = .016 vs IMP3). In all cases, the anesthesia was effective for at least 3 hours. LIMITATIONS: Results of this trial cannot be generalized to other local anesthetics such as prilocaine, bupivacaine, or ropivacaine, which precipitate with NaHCO3 admixtures. CONCLUSIONS: Lido/Epi-NaHCO3 mixtures effectively reduce burning pain during infiltration. The 3:1 mixing ratio is significantly less painful than the 9:1 ratio. Reported findings are of high practical relevance, given the extensive use of local anesthesia today.

The Headache Pipeline: Excitement and Uncertainty.

There are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. Farther out, three novel dihydroergotamine delivery systems, and a liquid-filled capsule of celecoxib show early promise. A new, safer form of methysergide is in the works, as is a longer-duration onabotulinumtoxinA. As always with new products, questions regarding safety, tolerability, cost, and insurance coverage will need to be addressed. Despite these concerns and uncertainties, a robust headache treatment pipeline is good for patients who are not satisfied with the results of their treatment and/or cannot tolerate existing treatments.

Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial.

BACKGROUND: Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis. METHODS: LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned. DISCUSSION: This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis. TRIAL REGISTRATION: clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

IMPACT OF LOCAL INFILTRATION ANESTHESIA ON POSTOPERATIVE PAIN MANAGEMENT AFTER RHINOPLASTY IN DAY CARE SURGERY.

Use of local infiltration anaesthesia with 2% lidocaine in combination with epinephrine 1/100000 in rhinoplasty and 0.25% levobupivacaine in this research as an adjunct to general anaesthesia is compared analysing the need for postoperative analgesia in rhinoplasty patients. 30 patients received lidocaine combined with epinephrine (LA) and other 30 patients received levobupivacaine (LB). Comparison is done with Visual Analogue Scale in 30 min and 1, 3, 6 h postoperatively. Also 24 h need for analgesic treatment was recorded. In conclusion postoperative analgesia in LB group with general anaesthesia was significantly prolonged (P = 0.038).

Effect of acute dietary nitrate supplementation on sympathetic vasoconstriction at rest and during exercise.

Dietary nitrate ( NO3- ) supplementation has been shown to reduce resting blood pressure. However, the mechanism responsible for the reduction in blood pressure has not been identified. Dietary NO3- supplementation may increase nitric oxide (NO) bioavailability, and NO has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle. Therefore, the purpose of this study was to investigate the hypothesis that acute dietary NO3- supplementation would attenuate sympathetic vasoconstrictor responsiveness at rest and during exercise. In a double-blind randomized crossover design, 12 men (23 ± 5 yr) performed a cold-pressor test (CPT) at rest and during moderate- and heavy-intensity alternate-leg knee-extension exercise after consumption of NO3- rich beetroot juice (~12.9 mmol NO3- ) or a NO3- -depleted placebo (~0.13 mmol NO3- ). Venous blood was sampled before and 2.5 h after the consumption of beetroot juice for the measurement of total plasma nitrite/ NO3- [NOx]. Beat-by-beat blood pressure was measured by Finometer. Leg blood flow was measured at the femoral artery via Doppler ultrasound, and leg vascular conductance (LVC) was calculated. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in LVC in response to the CPT. Total plasma [NOx] was greater (P < 0.001) in the NO3- (285 ± 120 µM) compared with the placebo (65 ± 30 µM) condition. However, mean arterial blood pressure and plasma catecholamines were not different (P > 0.05) between NO3- and placebo conditions at rest or during moderate- and heavy-intensity exercise. Sympathetic vasoconstrictor responsiveness (Δ% LVC) was not different (P > 0.05) between NO3- and placebo conditions at rest ( NO3- : -33 ± 10%; placebo: -35 ± 11%) or during moderate ( NO3- : -18 ± 8%; placebo: -20 ± 10%)- and heavy ( NO3- : -12 ± 8%; placebo: -11 ± 9%)-intensity exercise. These data demonstrate that acute dietary NO3- supplementation does not alter sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males. NEW & NOTEWORTHY Dietary nitrate may increase nitric oxide bioavailability, and nitric oxide has been shown to attenuate sympathetic vasoconstriction in resting and contracting skeletal muscle and enhance functional sympatholysis. However, the effect of dietary nitrate on sympathetic vasoconstrictor responsiveness is unknown. Acute dietary nitrate supplementation did not alter blood pressure or sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males.

A randomized controlled trial of trigger finger release under digital anesthesia with (WALANT) and without adrenaline.

BACKGROUND: Trigger finger release utilizing wide-awake local anesthesia no tourniquet (WALANT) usage in extremity surgery is not widely used in our setting due to the possibility of necrosis. Usage of a tourniquet is generally acceptable for providing surgical field hemostasis. We evaluate hemostasis score, surgical field visibility, onset and duration of anesthesia, pain score, and the duration of surgery and potential side effects of WALANT. METHODS: Eighty-six patients scheduled for trigger finger release between July 2016 and December 2017 were randomized into a control group (1% lignocaine and 8.4% sodium bicarbonate with arm tourniquet; given 10 min prior to procedure) and an intervention group (1% lignocaine, 1:100,000 of adrenaline and 8.4% sodium bicarbonate; given 30 min prior to procedure), with a total of 4 ml of solution injected around the A1 pulley. The onset of anesthesia and pain score upon injection of the first 1 ml were recorded. After the procedure, the surgeon rated for the hemostasis score (1-10: 1 as no bleeding and 10 being profuse bleeding). Duration of surgery and return of sensation were recorded. RESULTS: Hemostasis score was grouped into visibility score as 1-3: good, 4-6: moderate, and 7-10: poor. The intervention group (with adrenaline) had a 74% of good surgical field visibility compared to 44% from the controlled group (without adrenaline; p < 0.05). Duration of anesthesia was longer in the intervention group (with adrenaline), with a 2.77-h difference. CONCLUSION: WALANT provides excellent surgical field visibility and is safe and on par with conventional methods but without the usage of a tourniquet and its associated discomfort.

Wide-Awake Surgical Management of Hand Fractures: Technical Pearls and Advanced Rehabilitation.

Most unstable metacarpal and phalangeal fractures for which operative treatment is indicated can be reduced and stabilized with either open or closed techniques using local anesthetic with epinephrine instead of intravenous sedation or general anesthesia. With the patient wide-awake during surgery, the hand can be taken through active range of motion to assess fracture stability. In this article, the authors review the rationale and technique for wide-awake, local anesthesia, no tourniquet surgery in the treatment of phalangeal and metacarpal fractures and impart pearls to optimize the patient experience and illustrate common fixation techniques using percutaneous Kirschner wires. The intraoperative assessment of fracture stability permits an accelerated, protected-range-of-motion protocol that minimizes postoperative stiffness and facilitates expedient recovery.

Development and in vitro/in vivo evaluation of dihydroergotamine mesylate loaded maltodextrin-pullulan sublingual films.

Dihydroergotamine mesylate (DHE), ergotamine derivative, has been offered for clinical use to stop or treat symptoms of an emerging migraine as injection for more than a half century. It is shown that bioavailability of DHE greatly changes between the subjects and up to 99% of the orally absorbed dose may be cleared by first pass metabolism. The aim of this study was to design and optimize DHE fast-dissolving sublingual films for migraine treatment. For this purpose pullulan and maltodextrin was chosen as film-forming polymers and propylene glycol as plasticizer. For optimization process Box Behnken design was used. The formed films were free from air bubbles, cuttings, or cracks. Disintegration, mechanical strength and dissolution of films were compared. It is found that pullulan and maltodextrin formed films with the most desired properties at the concentration of 1.5% and 2%. The application of optimum formulation to rabbits showed that bioavailability of formulation is about 23.35% with a tmax 20 min. Due to this fast onset of action and higher bioavailability than oral administration, it is suggested that the polymer combinations of pullulan and maltodextrin formed successful films and were considered as an alternative dosage form for DHE in migraine therapy.

Onset Time of Local Anesthesia After Single Injection in Toe Nerve Blocks: A Randomized Double-Blind Trial.

PURPOSE: The study was conducted to investigate the onset time and safety profile of four different local anesthetic solutions. DESIGN: Randomized controlled clinical trial study. METHODS: One hundred twelve healthy volunteers were assigned to receive digital block on their second toe. Individuals were randomly assigned to one of the following groups: lidocaine 2%, lidocaine 2% with epinephrine, bupivacaine 0.5%, or bupivacaine 0.5% with epinephrine. Onset time was measured until detecting the absence of pinprick sensation. Oxygen saturation was measured in the infiltrated toe up to 60 minutes. FINDINGS: The subjects in the groups of anesthetics with epinephrine had a significantly lower mean onset time. There were no significant differences regarding oxygen saturation between the groups and no adverse effects were recorded. CONCLUSIONS: The use of anesthetics with epinephrine can be an effective form of local anesthetic for digital blocks when a rapid onset of action, prolonged duration of anesthesia, and vasoconstrictive action are required.