Incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery: a multi- center prospective observational study.

BACKGROUND: Failed spinal anaesthesia causes prolonging of operation time, insufficient analgesia for surgery and needs repeating spinal anaesthesia which in turn causes local anaesthesia toxicity, high spinal and total spinal, and conversion to general anaesthesia. However, the problem remains unexplored in Amhara regional state comprehensive specialized hospitals. OBJECTIVE: To determine incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery in selected Amhara National Regional State comprehensive specialized hospitals, Northwest Ethiopia, 2023. METHODS: Multi-center prospective observational study was conducted. Data was collected using questionnaire and checklist. All consecutive scheduled emergency and elective patients were included in the study. Data was transformed from Epi data to SPSS and logistic regression analysis was done. Both crude and adjusted odds ratio were used to assess the strength of association. Variables with a p-value of less than 0.05 were considered as statistically significant. RESULTS: A total of 532 patients were included in this study with a response rate of 98%. Incidence of failed spinal anaesthesia was 22.4% (CI = 19-25.9). Emergency surgery (AOR = 7.01, CI = 4.5-12.7), dose of bupivacaine of ≤ 10 mg (AOR = 3.02, CI = 1.3-10.2), work experience of anaesthetist < 2 years (AOR = 3.1, CI = 1.7-5.72), bloody CSF (AOR = 8.5, CI = 2.53-18.5), hyperbaric local anaesthetic drug (AOR = 3.3, 95% CI = 3.2-8.2) and local anaesthetist without adjuvants (AOR = 5.25, CI = 2.62-14.2) were associated failed spinal anaesthesia. CONCLUSION AND RECOMMENDATION: The incidence of failed spinal anaesthesia was high in Amhara Region comprehensive specialized hospitals. We suggest that anaesthesia providers should minimize failure by using adjuvants and appropriate dose of local anaesthetic. Additionally, simulation training should be given for anaesthesia trainees to improve their skills and to produce competent professionals.

The Anaesthetic Efficacy of Tetracaine and Oxymetazoline Compared With Co-Phenylcaine in Healthy Individuals.

OBJECTIVES: Nasal anaesthetic-decongestant sprays are commonly used prior to nasal instrumentation, such as flexible and rigid nasal endoscopy. Co-phenylcaine (lignocaine 5%, phenylephrine 0.5%, ENT Technologies Pty Ltd., Melbourne, VIC, Australia) is a combination spray commonly used for this purpose. However, lignocaine is less potent than other local anaesthetics, and both active constituents of Co-phenylcaine have a bitter taste. It was hypothesised that a combination spray containing tetracaine and oxymetazoline would both offer more potent topical anaesthesia and have a better taste. METHODS: Four anaesthetic-decongestant nasal sprays were tested in 10 healthy participants (Co-phenylcaine, and tetracaine 0.5%, 1% and 2% with oxymetazoline 0.05%). Sensory thresholds were sequentially measured at the head of the inferior turbinate using Semmes-Weinstein monofilaments over the following hour. Participants also rated taste on a Likert-style scale, and reported whether they experienced subjective numbness of the maxillary teeth. RESULTS: A median peak sensory threshold of 60 g (the maximum tested) was observed with Co-phenylcaine, but this threshold was exceeded by all the tetracaine-based sprays. Tetracaine 2% with oxymetazoline 0.05% had a significantly more rapid onset than Co-phenylcaine (4 min vs. 6 min, p < 0.05) and a longer duration of action. Eight participants reported dental numbness after administration of tetracaine 2% with oxymetazoline 0.05%, but only one participant after Co-phenylcaine. Tetracaine-based sprays were generally perceived to taste less unpleasant than Co-phenylcaine. CONCLUSION: Tetracaine 2% with oxymetazoline 0.05% is a more potent and rapidly acting anaesthetic-decongestant spray than Co-phenylcaine, with a longer duration of action.

Assessing knowledge of dental house officers regarding dosage calculation and complications of local anaesthesia, in three tertiary care dental hospitals of DUHS, Karachi.

Objectives: To assess the knowledge and awareness of dental house officers regarding calculation of local anaesthesia dosage, and to evaluate differences in practices at various tertiary care facilities. METHODS: The cross-sectional study was conducted at three dental hospitals affiliated with Dow University of Health Sciences, Karachi from July to December 2022, and comprised house officers of either gender currently enrolled at the participating centres. Data was collected using a self-administered questionnaire to assess knowledge and awareness of local anaesthesia dosage calculation, administration methods, and common complications. Data was analysed using SPSS 26. RESULTS: Of the 200 subjects approached, 136(68%) responded, and 89(65.4%) of them were females. Knowledge regarding the meaning of 2% lidocaine solution was low 45(33%), and 68(50%) subjects were knowledgeable about the maximum dosage of lidocaine with epinephrine. In terms of practice, lidocaine was the most commonly administered local anaesthetic 115(85%), followed by bupivacaine 15(11%). The majority of subjects administered local anaesthesia with vasoconstrictor 127(94%), but only 36(27%) performed aspiration during administration. Syncope 71(52%) was the most commonly reported complication, followed by lip/cheek/tongue biting by 35(26%). CONCLUSIONS: House officers' knowledge level of local anaesthesia administration indicated the need for adequate training.

Intravenous Lipid Emulsion does NOT have a role in severe poisoning: CON.

Intravenous lipid emulsion (ILE) has been suggested as a potential universal antidote for cardiovascular and central nervous system toxicity resulting from a multitude of pharmaceutical and nonpharmaceutical poisonings. While there is some evidence to suggest that ILE may have a positive effect in cardiovascular system toxicity after accidental intravenous lipophilic local anaesthetic overdose, this cannot be extrapolated to cases of severe poisoning resulting from oral drug overdose. Treatment recommendations are based upon variable outcome animal studies and low-level clinical evidence with a significant degree of positive reporting bias. Currently, there is a paucity of controlled clinical data to support ILE use to treat severe drug poisoning after oral overdose. ILE use should be limited to well-designed, ethically approved, controlled clinical trials aimed at determining the true effectiveness of this therapy. This should replace the current scattergun clinical use in a multiplicity of poisoning scenarios and subsequent anecdotal reporting approach.

The Local Anaesthetic Procaine Prodrugs ProcCluster® and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro.

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster® and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed.

Intraoperative Epidural Analgesia Practices And Their Outcomes In Major Abdominal Surgeries At A Tertiary Care Hospital In Karachi.

OBJECTIVE: To investigate the association involving site, concentrations and dosing of local anaesthetics used intraoperatively on postoperative pain scores, motor block and need for rescue analgesia. METHODS: The observational study was conducted from June 1, 2020, to May 31, 2021, at the Aga Khan University Hospital, Karachi, and comprised patients planned for major abdominal surgeries with epidurals as primary analgesic modality. They were followed prospectively from placement of epidurals to 24h postoperatively. Data was collected from anaesthesia chart and pain management notes. Data was analysed using SPSS 19. RESULTS: Of the 170 patients, 96(56.4%) were females and 74(43.5%) were males. The overall mean age was 54.1±12.6 years and mean body mass index was 26.7±5.5Kg/m2. More than half of the patients 110(64.7%) had thoracic epidural, while 60(35.3%) had lumber epidural. Requirement of opioid co-analgesia intraoperatively was significantly high with higher compared to lower concentration of local anaesthetics (p=0.004). The difference in frequencies of motor block was significantly associated with catheter length (p=0.006). CONCLUSIONS: Intraoperative management of epidurals is an essential but overlooked component of perioperative pain management. Guidelines should be formulated for intraoperative epidural analgesic regimens to improve postoperative outcomes.

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

The effect of intraperitoneal ropivacaine on post-operative pain and recovery after diagnostic laparoscopy and hysteroscopy: A randomised double-blind placebo-controlled trial.

BACKGROUND: Intraperitoneal local anaesthetic has shown benefit in operative laparoscopy; however, no randomised controlled trial has been reported with patients having diagnostic laparoscopy. AIMS: To determine the effect of intraperitoneal ropivacaine on post-operative analgesic requirements, pain, nausea scores and recovery following gynaecological diagnostic laparoscopy and hysteroscopy. MATERIALS AND METHODS: Randomised double-blind placebo-controlled trial. Well women aged 18-50 years, undergoing day case hysteroscopy and diagnostic laparoscopy for gynaecological indications were randomised to 20 mL of 150 mg intraperitoneal ropivacaine diluted in saline, or 20 mL normal saline instillation (placebo) at the end of the procedure. Women were followed up until eight hours post-discharge. RESULTS: Slower than anticipated recruitment meant that the study was finished before the sample size of 100 patients was achieved. Fifty-nine patients were included for analysis. Thirty-one patients were randomised to ropivacaine and 28 patients to control. Sixty-one percent of patients in both arms required opioid medication in recovery. The total median equivalent morphine dose was significantly higher in the patients randomised to control (11.7 mg) vs ropivacaine (6.7 mg), P = 0.03. Time to discharge was 20 min faster in patients randomised to ropivacaine, but this finding did not reach significance. Overall pain and nausea scores in the first eight hours showed no significant differences. CONCLUSION: There was significantly reduced opioid use in recovery when using intraperitoneal ropivacaine compared to placebo, in this randomised placebo-controlled trial on women undergoing day case diagnostic laparoscopy and hysteroscopy.

The effectiveness of repetitive paravertebral block with ropivacaine and dexmedetomidine for the prevention of postherpetic neuralgia in patients with acute herpes zoster.

Introduction: Herpes zoster (HZ) is a disease caused by the reactivation of the varicella zoster virus. Postherpetic neuralgia (PHN) is the most common complication of HZ. Aim: Repetitive paravertebral block with local anaesthetics and dexmedetomidine for the prevention of PHN in patients with acute herpes zoster. Material and methods: 104 patients with acute herpes zoster were randomly divided into two groups. Group Rop received repetitive paravertebral block with 0.25% ropivacaine 20 ml per 72 h three times. Group Dex received repetitive paravertebral block with a mixture of 0.25% ropivacaine 20 ml and dexmedetomidine 20 µg per 72 h three times. Patients were permitted to take tramadol when the visual analogue scale (VAS) ≥ 4. The incidence of zoster-related pain was recorded at 1, 3, and 6 months after the end of treatments; VAS scores and the dose of rescue drug were recorded at 1 week, 2 weeks, 1 month, 3 months, and 6 months after the end of treatments. Results: At 1 month post therapy, the incidence of zoster-related pain was 11% in Group Dex, compared with 35% in Group Rop (p = 0.005). At 3 months post therapy, the incidence of zoster-related pain in Group Dex was still significantly lower than in Group Rop. The VAS scores and the dose of rescue drug in Group Dex were also significantly lower than in Group Rop at each time point (p < 0.05). Conclusions: Repetitive paravertebral block with local anaesthetics and dexmedetomidine in patients with acute herpes zoster can significantly reduce the incidence of zoster-related pain.

Local anaesthetic adjuncts for peripheral regional anaesthesia: a narrative review.

Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the routine use of regional anaesthesia techniques. The administration of local anaesthetic adjuncts, defined as the concomitant intravenous or perineural injection of one or more pharmacological agents, is an attractive and technically simple strategy to potentially extend the benefits of peripheral nerve blockade beyond the conventional maximum of 8-14 hours. Historical local anaesthetic adjuncts include perineural adrenaline that has been demonstrated to increase the mean duration of analgesia by as little as just over 1 hour. Of the novel local anaesthetic adjuncts, dexmedetomidine and dexamethasone have best demonstrated the capacity to considerably improve the duration of blocks. Perineural dexmedetomidine and dexamethasone increase the mean duration of analgesia by up to 6 hour and 8 hour, respectively, when combined with long-acting local anaesthetics. The evidence for the safety of these local anaesthetic adjuncts continues to accumulate, although the findings of a neurotoxic effect with perineural dexmedetomidine during in-vitro studies are conflicting. Neither perineural dexmedetomidine nor dexamethasone fulfils all the criteria of the ideal local anaesthetic adjunct. Dexmedetomidine is limited by side-effects such as bradycardia, hypotension and sedation, and dexamethasone slightly increases glycaemia. In view of the concerns related to localised nerve and muscle injury and the lack of consistent evidence for the superiority of the perineural vs. systemic route of administration, we recommend the off-label use of systemic dexamethasone as a local anaesthetic adjunct in a dose of 0.1-0.2 mg.kg-1 for all patients undergoing surgery associated with significant postoperative pain.

Supraclavicular block with Mepivacaine vs Ropivacaine, their impact on postoperative pain: a prospective randomised study.

BACKGROUND: Supraclavicular block (SCB) with long-acting local anaesthetic is commonly used for surgical repair of distal radial fractures (DRF). Studies have shown a risk for rebound pain when the block fades. This randomised single-centre study aimed to compare pain and opioid consumption the first three days post-surgery between SCB-mepivacaine vs. SCB-ropivacaine, with general anaesthesia (GA) as control. METHODS: Patients (n = 90) with ASA physical status 1-3 were prospectively randomised to receive; SCB with mepivacine 1%, 25-30 ml (n = 30), SCB with ropivacaine 0.5%, 25-30 ml (n = 30) or GA (n = 30) with propofol/fentanyl/sevoflurane. Study objectives compared postoperative pain with Numeric Rating Scale (NRS) and sum postoperative Opioid Equivalent Consumption (OEC) during the first 3 days post-surgery between study-groups. RESULTS: The three groups showed significant differences in postoperative pain-profile. Mean NRS at 24 h was significantly lower for the SCB-mepivacaine group (p = 0.018). Further both median NRS and median OEC day 0 to 3 were significanly lower in the SCB-mepivacaine group as compared to the SCB-ropivacaine group during the first three days after surgery; pain NRS 1 (IQR 0.3-3.3) and 2.7 (IQR 1.3-4.2) (p = 0.017) and OEC 30 mg (IQR 10-80) and 85 mg (IQR 45-125) (p = 0.004), respectively. The GA-group was in between both in pain NRS and median sum OEC. Unplanned healthcare contacts were highest among SCB-ropivacaine patients (39.3%) vs. SCB-mepivacaine patients (0%) and GA-patients (3.4%). CONCLUSIONS: The potential benefit of longer duration of analgesia, associated to a long-acting local anaesthetic agent, during the early postoperative course must be put in perspective of potential worse pain progression following block resolution. TRIAL REGISTRATION: NCT03749174 (clinicaltrials.gov, Nov 21, 2018, retrospectively registered).

A computed tomography-based method for the assessment of canine retrobulbar cone volume for ophthalmic anaesthesia.

OBJECTIVE: To develop a comprehensive formula for calculating the volume of local anaesthetic solution used for retrobulbar anaesthesia in dogs with different skull morphologies. STUDY DESIGN: Retrospective cohort imaging study. ANIMALS: Skull computed tomography (CT) images of 188 dogs of different breeds collected between January 2009 and December 2017. METHODS: Anatomical integrity of the orbit and adjacent structures, presenting complaint, clinical signs and CT findings were verified to exclude ocular abnormalities. The volume of the retrobulbar cone of 376 eyes was calculated using CT scans of the dogs' skulls. Additional data recorded included morphology of the skull, body weight, sex and size of the dogs, all of which were matched for possible association to the retrobulbar cone volume through univariable and multivariable linear regression models. Results of linear regression models were expressed as estimated beta coefficients with the corresponding 95% confidence intervals (95% CIs). RESULTS: Using univariate analysis, the retrobulbar cone volume was positively associated with weight and male sex. In addition, brachycephalic and dolichocephalic dogs showed a larger retrobulbar cone volume than mesocephalic dogs, while sex was no longer significantly associated with the retrobulbar cone volume. In multivariate analysis, when considering all variables in the model, weight emerged as the strongest predictor (beta coefficient: 0.062 mL kg-1, 95% CI: 0.056-0.067 mL kg-1, p < 0.001). CONCLUSIONS: and clinical relevance In the veterinary literature, there is no agreement on the precise volume of local anaesthetic solution that should be used to achieve intraconal retrobulbar anaesthesia in dogs. Here we suggest a formula to calculate the retrobulbar cone volume and, accordingly, the injection volume of local anaesthetic solution for effective retrobulbar anaesthesia.

Adverse reaction to local anaesthetics: Is it always allergy?

OBJECTIVE: Local anaesthetics are very commonly used drugs in dentistry, and people who undergo procedures with local anaesthetics often refer adverse reactions that are not of allergic origin. Considering that in dentistry contact with allergens is very frequent, it is essential to assess the real incidence of allergy to local anaesthetics. SUBJECTS AND METHODS: We evaluated a group of 159 patients in whom adverse reaction occurred after procedures with local anaesthetics. RESULTS: The reactions between allergy to local anaesthetic (immediate and delayed) and certain symptoms presented by patients were investigated. Allergy to latex and chlorexidine were investigated in all patients. Only one patient, who previously presented a constant erythema at the wrist after procedure with local anaesthetics, was positive to Mepivacaine patch test. Two patients were positive to latex and one to chlorexidine. CONCLUSIONS: The main finding of this study was that a reaction registered in the medical history and reported by a patient is rarely allergic but the use of vasoconstrictors or emotional factors may account for it. However, a complete allergological investigation is necessary for a correct diagnosis and future management.

Choice of local anaesthetic for epidural caesarean section: a Bayesian network meta-analysis.

Rapid-onset epidural local anaesthesia can avoid general anaesthesia for caesarean delivery. We performed a Bayesian network meta-analysis of direct and indirect comparisons to rank speed of onset of the six local anaesthetics most often used epidurally for surgical anaesthesia for caesarean delivery. We searched Google Scholar, PubMed, EMBASE, Ovid, CINAHL and CENTRAL to June 2019. We analysed 24 randomised controlled trials with 1280 women. The mean (95%CrI) onset after bupivacaine 0.5% was 19.8 (17.3-22.4) min, compared with which the mean (95%CrI) speed of onset after lidocaine 2% with bicarbonate, 2-chloroprocaine 3% and lidocaine 2% was 6.4 (3.3-9.6) min faster, 5.7 (3.0-8.3) min faster and 3.9 (1.8-6.0) min faster, respectively. Speed of onset was similar to bupivacaine 0.5% after ropivacaine 0.75% and l-bupivacaine 0.5%: 1.6 (-1.4 to 4.8) min faster and 0.4 (-2.2 to 3.0) min faster, respectively. The rate (95%CrI) of intra-operative hypotension was least after l-bupivacaine 0.5%, 315 (236-407) per 1000, and highest after 2-chloroprocaine 3%, 516 (438-594) per 1000. The rate (CrI) of intra-operative supplementation of analgesia was least after ropivacaine 0.75% 48 (19-118) per 1000 and highest after 2-chloroprocaine 3%, 250 (112-569) per 1000.

Local anaesthesia for surgical extraction of mandibular third molars: a systematic review and network meta-analysis.

OBJECTIVES: Pain management for the extraction of the mandibular third molar is a challenge as compelling evidence in comparative anaesthetics is currently lacking. MATERIALS AND METHODS: Thorough literature searches took place in PubMed, ScienceDirect, CENTRAL, Embase, Web of Science, CBM, and CNKI. Thirty-three trials were meta-analysed using a Bayesian statistical approach within the random-effects model. Grading of Recommendations Assessment, Development, and Evaluation was performed to determine the overall quality of evidence across all comparisons. RESULTS: In terms of success rate, an inferior alveolar nerve block (IANB) injection of 2% lidocaine with epinephrine was less effective than a combined injection of buccal infiltration (BI) and lingual infiltration (LI) with a 4% articaine (RR = 0.85 [0.75, 0.96], P = 0.611). According to visual analogue scale (VAS), 2% lidocaine-IANB with epinephrine caused higher VAS scores than 4% articaine-IANB with epinephrine (MD = 0.84 [0.28, 1.40], P = 0.057), whereas 0.5% levobupivacaine-IANB showed lower scores than 2% lidocaine-IANB (MD = - 1.62 [- 2.97, - 0.28], P = 0.045). Also, 2% lidocaine-IANB with epinephrine presented longer latency than both 4% articaine-IANB with epinephrine (MD = 39.44 [16.97, 61.90], P < 0.001) and 4% articaine-BI + LI with epinephrine (MD = 164.41 [16.23, 312.58], P < 0.001); 4% articaine-IANB with epinephrine produced shorter latency than 0.5% bupivacaine-IANB with epinephrine (MD = - 42.92 [- 70.28, - 15.56], P = 0.106); 0.75% ropivacaine-IANB caused shorter onset of action compared with 2% lidocaine-IANB (MD = - 40.88 [- 65.50, - 16.26], P < 0.001). In addition, 2% lidocaine-IANB with epinephrine produced significantly shorter duration than both 4% articaine-IANB with epinephrine (MD = - 47.33 [- 57.88, - 36.77], P = 0.265) and 2% mepivacaine-IANB with epinephrine (MD = - 10.01 [- 19.59, - 0.44], P = 0.769). The duration of action triggered by 4% articaine-IANB with epinephrine was shorter compared with 0.5% bupivacaine-IANB with epinephrine (MD = - 64.17 [- 74.65, - 53.69], P = 0.926). Both 0.5% levobupivacaine-IANB and 0.75% ropivacaine-IANB produced longer duration of action than 2% lidocaine-IANB (MD = 333.70 [267.33, 400.07], P < 0.001) and (MD = 288.01 [287.67, 288.34], P = 0.634, respectively). CONCLUSIONS: The network meta-analysis demonstrated that the intraosseous injection of 4% articaine with epinephrine had the most noteworthy success rate. However, the combination of BI and LI of 4% articaine with epinephrine, and IANB of 0.5% bupivacaine were, according to a VAS, the most effective. It should be noted that a rapid onset of action was produced by BI combined with LI of 4% articaine with epinephrine and IANB of 2% mepivacaine with epinephrine, while the most prolonged duration of action was generated by IANB of 0.5% levobupivacaine or 0.5% bupivacaine. CLINICAL RELEVANCE: For a better understanding of local anaesthesia for the extraction of the third molar, our study was aimed to provide evidence to guide better dental practices in pain management for clinicians.

Efficacy and cardiorespiratory effects of lumbosacral intrathecal 2% procaine and 2% xylazine with or without sedation in calves undergoing umbilical surgery.

Aims: To compare the effects of intrathecal anaesthesia using procaine and xylazine, with and without sedation with I/V xylazine and butorphanol, on sedation and cardiorespiratory measures in calves undergoing umbilical surgery. Methods: Male dairy calves, aged <3 months, were recruited that had enlargement of the umbilical stalk which was abnormal when palpated. They were assigned to receive either intrathecal injection between the sixth lumbar and first sacral vertebrae of 4 mg/kg of 2% procaine and 0.2 mg/kg 2% xylazine, with I/V injection of 0.02 mg/kg xylazine and 0.1 mg/kg of butorphanol (IT + SED group; n = 6), or the same intrathecal injection and I/V injection of 0.9% saline (IT group; n = 7). Surgery to correct abnormalities was carried out with calves positioned in dorsal recumbency. Rescue analgesia with injections of 2% procaine around the surgical wound was administered when movements triggered by surgery were observed. Post-operative analgesia was provided using I/V 0.5 mg/kg meloxicam. Duration of surgery was recorded, as well as degree of sedation, heart rate, systolic (SAP), diastolic (DAP) and mean (MAP) arterial blood pressure during surgery. Results: All anaesthetic and surgical procedures were successfully performed. Mean total duration of surgery was similar for the IT + SED and the IT groups (30.33 (SD 10.09) and 31.00 (SD 10.21) minutes, respectively) (p = 0.92). All calves were at least mildly sedated from 5 minutes after injections to the end of the surgery. One calf in the IT + SED group and three calves in the IT group required rescue analgesia when the umbilicus was manipulated. Between 0 and 10-15 minutes after injection, decreases in mean heart rate, SAP, MAP and DAP were observed in both groups. Mean SAP was lower in the IT + SED than the IT group. Hypotension (MAP<60 mm Hg) was present in four calves from the IT + SED group and in one from the IT group. Conclusions and clinical relevance: Intrathecal administration of 2% procaine and 2% xylazine allowed the successful completion of umbilical surgery, but 30% of calves needed rescue analgesia during surgery. Clinically, the addition of I/V sedation seemed to provide better analgesia than intrathecal block alone but resulted in greater hypotension.

Post-operative pain after laparoscopic ventral hernia repair, the impact of mesh soakage with bupivacaine solution versus normal saline solution: A randomised controlled trial (HAPPIEST Trial).

BACKGROUND AND AIMS: Early postoperative pain after laparoscopic ventral hernia repair remains a concern for patients. Local application of anaesthetic agent in the surgical dissection area can potentially overcome this problem. The objective of this study was to evaluate the impact of soaking mesh in 0.5% bupivacaine solution as compared to normal saline solution on the post-operative pain. METHODOLOGY: We conducted a parallel-design double-blind randomised controlled trial. Adult patients with uncomplicated ventral abdominal wall hernias were included in the trial. Mesh was soaked in 0.5% solution of bupivacaine before application in patients in the intervention arm, whereas it was soaked in normal saline solution for patients in the control arm. Post-operative pain was assessed by trained staff at 6 h and 24 h from surgery. It was graded on visual analogue scale (VAS) from 0 to 10. RESULTS: Trial was conducted from 16 November, 2015, to 15 September, 2017. During the study period, a total of 114 patients were randomised. Nine patients were excluded after randomisation. A total of 55 patients were analysed in the intervention arm and 50 patients were analysed in the control arm. Mean pain score at VAS at 6 h after laparoscopic ventral hernia repair in the intervention arm was 5.05 ± 1.2, whereas in the control arm, it was 5.54 ± 1.1 and the difference was statistically significant (P = 0.03-independent sample t-test). Mean pain score at VAS at 24 h after laparoscopic ventral hernia repair in the intervention arm was 3.16 ± 1.2, whereas in the control arm, it was 3.58 ± 1.4 and the difference was not statistically significant (P = 0.11-independent sample t-test). CONCLUSION: Soakage of mesh in 0.5% bupivacaine solution before application in laparoscopic ventral hernia repair significantly reduces early post-operative pain. TRIAL REGISTRATION: Trial was registered with clinicaltrials. gov (NCT03035617)URL: https://clinicaltrials. gov.

Viability and intracellular nitric oxide generation in the umbilical cord blood CD34+CD133- and CD34+CD133+ cell populations exposed to local anaesthetics.

Local anesthetics (LAs) are capable of influencing cell viability in systemic immunity and may also modify metabolism of those present in umbilical cord blood (UCB) following obstetric neuraxial analgesia and anaesthesia. Data regarding UCB immature cells, important for the neonate and critical for putative UCB transplantations, are lacking. LAs are capable of stimulating intracellular nitric oxide (NO) in human neutrophils; no information is available concerning newly perpetuated cells and its potential association with viability. The study aimed at assessing the LAs influence on the cell viability and intracellular NO production by UCB CD34+CD133- and CD34+ CD133+ cell populations. Mononuclear cells separated from UCB samples (n = 19) were incubated with bupivacaine (0.0005, 0.005, 1 mM), lidocaine (0.002, 0.02, 4 mM), and ropivacaine (0.0007, 0.007, 1.4 mM) for 4 h. Flow cytometry was applied for the assessment of cell viability and intracellular NO generation in CD34+CD133- and CD34+CD133+ cell populations using annexinV/7-AAD and DAF-2DA stainings, respectively. CD34+CD133+ cells showed less pronounced late apoptosis and necrosis as compared to CD34+CD133-population. Intracellular NO generation was comparable between both cell populations studied. LAs neither influenced cell viability nor changed NO production in either population. LAs do not interfere with viability and intracellular NO generation in the UCB CD34+CD133- and CD34+CD133+ cell populations.

Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised, triple-blinded crossover study in volunteers.

BACKGROUND: The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine. METHODS: Ultrasound-guided ulnar nerve blocks (ropivacaine 0.75% wt/vol, 3 ml, with saline 1 ml with or without dexamethasone 4 mg) were performed on three occasions in 24 male volunteers along with an i.v. injection of saline 1 ml with or without dexamethasone 4 mg. The combinations of saline and dexamethasone were as follows: control group, perineural and i.v. saline; perineural group, perineural dexamethasone and i.v. saline; i.v. group, perineural saline and i.v. dexamethasone. Sensory block was measured using a VAS in response to pinprick testing. The duration of sensory block was the primary outcome and time to onset of sensory block the secondary outcome. RESULTS: All 24 subjects completed the trial. The median [inter-quartile range (IQR)] duration of sensory block was 6.87 (5.85-7.62) h in the control group, 7.37 (5.78-7.93) h in the perineural group and 7.37 (6.10-7.97) h in the i.v. group (P=0.61). There was also no significant difference in block onset time between the three groups. CONCLUSION: Dexamethasone 4 mg has no clinically relevant effect on the duration of sensory block provided by ropivacaine applied to the ulnar nerve. CLINICAL TRIAL REGISTRATION: DRKS, 00014604; EudraCT, 2018-001221-98.

Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review.

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.