Physiological Variables for Nerve Block Failure in Dogs PDF

Veterinary Anaesthesia and Analgesia 2024, 51, 343e353 https://doi.org/10.1016/j.vaa.2024.03.010 RESEARCH PAPER Physiological variables for the objective detection of nerve block failure in dogs Etienne P Bassona,b, Abdur R Kadwab, Christiaan J Blignautb & Gareth E Zeilera,b a Anaesthesia and Critical Care Services, Valley Farm Animal Hospital, Pretoria, South Africa b Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa Correspondence: Etienne P Basson, Valle Farm Animal Hospital, 829 Old Farm Rd, Faerie Glen, Pretoria, 0043, South Africa. E-mail: [email protected] Abstract Conclusions and clinical relevance Blood pressure values can detect a response to surgical stimulus in adequately Objective To identify physiological variables for objectively anaesthetized dogs. The use of DMAP, DSAP or DDAP may detecting nociception indicative of intraoperative peripheral be considered as objective measures to detect nerve block nerve block failure. failure. Study design A double-blinded randomized clinical study. Keywords analgesia, failure, intraoperative nociception, Animals A sample of 14 male (40.8 ± 12 kg; mean ± nerve block, physiological variables. standard deviation) and 16 female (34.3 ± 11.4 kg) client- owned dogs. Introduction Methods Dogs were randomly assigned to one of three Nociception is the process by which the peripheral and central groups for psoas compartment and proximal sciatic nerve nervous system encodes a noxious stimulus (Merskey & blocks (0.2 mL kge1 per site): guided bupivacaine (GBB), or Bogduk 1994). Post-anaesthetic pain because of the percep- saline (GSB) block or a blind bupivacaine block (BBB). tion of these encoded signals plays an integral role in post- Guided blocks were performed using an ultrasound- operative outcome. Concepts such as Enhanced Recovery After peripheral nerve locator combination. Premedication con- Surgery (ERAS) and fast-track surgery focus on abbreviating sisted of medetomidine 0.01 mg kge1 and morphine 0.3 mg the time to full recovery. Peripheral nerve blocks play an kge1. General anaesthesia was induced with propofol and important role in ERAS (Campoy 2022). There is a correlation maintained with isoﬂurane in oxygen. Receiver operator between the intensity of the immediate postoperative pain and characteristic curve analysis was used to compare actual the development of persistent (maladaptive) pain (Kehlet et al. values and change in values of physiological variables be- 2006). Therefore, the importance of detecting nerve block tween GSB and GBB. The Youden index and associated failure intraoperatively prior to the recovery period is apparent. criterion for each physiological variable were used to The change in physiological variables relating to the auto- determine an objective measure for nociception. Fisher’s nomic nervous system (ANS) forms the basis of several exact t test, McNemar’s test and Cohen’s kappa statistical methods used for the assessment of nociception. Nociception analysis were used to determine association, differences and results in an increased sympathetic tone (Miller & O’Callaghan inter-score reliability between the objective and subjective 2002) which is mostly as a result of the intersection of the scoring for BBB. sympathetic branch of the ANS and nociceptive pathways Results Cardiovascular variables had good discriminating (Benarroch 2006). Physiological variables [heart rate (HR), ability to identify a nociceptive response (p < 0.01). The arterial blood pressure (BP), respiratory rate (fR) and tidal Youden indices for mean (MAP) and diastolic (DAP) arterial volume (VT)] are still used subjectively to detect nociception in pressure were most reliable in detecting nociception. The humans (Stomberg et al. 2001). A 20% increase in mean highest sensitivity was that of DMAP (100%) with good arterial pressure (MAP) and HR has been used as criteria to agreement between the subjective and objective scores of determine peripheral nerve block failure in dogs (Papadopoulos Dheart rate or systolic arterial pressure (SAP). The use of et al. 2022). An increase in MAP is a sensitive indicator of DMAP, DSAP, DDAP had the best ability in indicating pe- nociception in isoﬂurane-anaesthetized pigs and horses (Haga ripheral nerve block failure (p < 0.001). et al. 2001; Haga & Dolvik 2005). Derivatives of physiological 343 Detecting peripheral nerve block failure EP Basson et al. variables have been used to create objective measures for available except during the immediate perioperative period. assessing the absence of nociception. The most common of The study was approved by the Animal Ethics Committee of the these is heart rate variability (HRV) which has been assessed in University of Pretoria (V035-17). dogs (Bergfeld et al. 2014). Algorithms that incorporate different combinations of HR, BP responses, HRV, pulse beat Study design interval and pulse wave amplitude have also been developed. A prospective double-blinded randomized clinical trial was The cardiovascular depth of analgesic (CARDEAN) index planned. The study complied with CONSORT guidelines. Pop- makes use of pulse oximetry, electrocardiogram and oscillo- ulation sampling was opportunistic, following informed client metric BP measurements (Rossi et al. 2012). The perfusion consent. Randomization was achieved by means of an online index uses the waveforms of the plethysmograph to analyse balanced block randomization technique (two investigators, pulse interval and amplitude (Bonhomme et al. 2011; three groups; Sealed Envelope Ltd., UK). Dogs were randomly Bergmann et al. 2013). Perfusion index has been used to assigned to one of two investigators and one of three groups: determine peripheral nerve block success in dogs (Gatson et al. guided bupivacaine block (GBB), guided saline block (GSB) or 2016) Pupillometry assesses the ANS tone by means of an blind bupivacaine block (BBB). The second block for random- infrared pupillometer (Mills et al. 2022). Despite all these as- ization (group) was only known by the assigned investigator. sessments, there is still no consensus on how to objectively The other investigator assigned to recording the variables was conﬁrm nociception, especially in anaesthetized veterinary blinded to the allocated group. The study was divided into two patients (Ledowski 2019). parts (Fig. S1). There is need for a practical, objective way to detect intra- Part A: To evaluate commonly measured physiological operative nociception which is indicative of nerve block failure variables to detect if the magnitude of response to surgical and thereby prompt the veterinarian to administer analgesics stimulation between GSB and GBB groups was different. These before the animal recovers. physiological variables were used to objectively score nerve The aim of this study was to identify routinely measured block outcome. physiological variables that could be used to objectively detect Part B: To assess agreement of the objective score of nerve a response to surgical stimulus and therefore indicate intra- block outcome determined in part A with subjective and con- operative nerve block failure. The null hypothesis was that ﬁdence scoring. A BBB was performed and objective and sub- physiological variables would be no different between ultra- jective scores were assigned and agreement between them sound (US)-peripheral nerve locator (PNL)eguided blocks us- were assessed. ing saline compared with bupivacaine in anaesthetized dogs during arthrotomy. Sample size Materials and methods The sample size necessary for comparison of means was calculated at 10 dogs per group. MAP was used as the variable Animals and housing of interest for the calculation by applying these assumptions: type I error of 0.05, type II error of 0.20, difference of means of A sample of 30 client-owned dogs of different breeds that were 4 mmHg and standard deviation of 3 mmHg. to undergo an arthrotomy and dynamic cranial cruciate liga- ment repair were included in the study after informed owner Experimental procedures consent. Inclusion criteria were dogs weighing 20 kg with unilateral pathology of a stiﬂe joint requiring an arthrotomy The dogs were starved of food for 6 hours prior to premed- and deemed healthy based on clinical examination and routine ication. The order and timing of procedures was standardized haematology and serum biochemistry assessments (American (Fig. S2). Premedication consisted of medetomidine 0.01 mg Society Anesthesiologists classiﬁcation score of I or II). Dogs kge1 (Domitor, 1 mg mLe1; Zoetis; RSA) and morphine 0.3 mg that had radiographic evidence of concurrent osteoarthritic kge1 (Morphine, 10 mg mLe1; Pharma-Q Holdings (Pty) Ltd., changes in any other joint of the pelvic limb or with concurrent RSA) mixed in one syringe and injected intramuscularly (IM). neurological disease were not included. Dogs were excluded if Dogs were left undisturbed for 15 minutes. An intravenous (IV) peripheral nerve blocks were contraindicated such as coagul- cannula (Jelco 20 G; Smiths Medical, UK) was aseptically opathy or infection at the nerve block site. Hypotension or placed and secured in one of the cephalic veins. At 30 minutes unsuccessful arterial cannulation were also used as exclusion after premedication, propofol 2e4 mg kge1 [Fresenius Propo- criteria. The study was conducted at Valley Farm Animal ven 1%; Fresenius Kabi (Pty) Ltd., RSA] was administered IV Hospital, Pretoria, Gauteng, RSA. The dogs were housed in until the trachea could be intubated with a cuffed 8.0e12 mm hospital cages and fed kibble twice a day and water was freely inner diameter polyvinyl endotracheal tube (ETT) (Ho-lee tube; 344 © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. JC Medical, RSA). The ETT was connected to a circle circuit Guided blocks were performed using US (Esaote MyLab-One; with a fresh gas (mixture of oxygen and medical air with an Lomaen Medical, RSA) with a 4e13 MHz linear transducer FIO2 of 0.5) ﬂow rate of 2 L minutee1. Anaesthesia was (Touch SL3323, Esaote MyLab-One; Lomaen Medical) in maintained using isoﬂurane in oxygen [Isofor; Safeline Phar- combination with a PNL (Stimpod NMS 450; Xavant Tech- maceuticals (Pty) Ltd., RSA] with the vaporizer (Penlon Sigma nology, RSA). On completion of the blocks, a timer was started Delta) initially set at 2% and titrated to an end-tidal isoﬂurane to count down from 60 minutes. A conﬁdence score of the concentration (FE0 Iso) of 1.6%. Perioperative antibiotics using block was recorded (Table 1) along with an assessment of the cefazolin [Zefkol, 100 mg mLe1; Litha Pharma (Pty) Ltd., RSA] ease of landmark palpation. Then the surgical site was shaved was administered IV at 20 mg kge1 after induction of anaes- and aseptically prepared. A cannula (Jelco 22 gauge; Smiths thesia and repeated every 90 minutes during anaesthesia. Medical) was aseptically introduced and secured in the dor- The dog was placed in lateral recumbency with the surgical sopedal artery contralateral to the operated limb being oper- pelvic limb in the non-dependent position. The block sites were ated. Once the surgical preparation was complete, the dog was clipped and aseptically prepared. The psoas compartment block moved to the theatre table and placed in dorsal recumbency. (Fig. 1a; Mahler 2012; Portela et al. 2013) was performed The dog was connected to the anaesthetic machine, as before the lateral proximal sciatic nerve block (Fig. 1b; Costa- described previously, and monitor sensors and leads were Farre et al. 2011). Injectate volume for all blocks was stan- attached. The invasive BP transducer [Sembu TR transducers; dardized at 0.2 mL kge1. Saline (Sodium Chloride 0.9%; Fre- SSEM Mthembu Medical (Pty) Ltd, RSA] was zeroed to atmo- senius Kabi) was administered for GSB and bupivacaine spheric pressure at the level of the sternal manubrium. A fast- (Macaine 5 mg mLe1; Adcock Ingram, RSA) for GBB and BBB. ﬂush test was performed to subjectively ensure adequate Figure 1 Ultrasound and peripheral nerve locatoreguided psoas compartment (a) and lateral proximal sciatic (b) nerve block being performed on a dog. Ultrasound images obtained are shown on the right. External iliac artery (EIA), seventh lumbar vertebral body (VB) and its transverse process (TP), femoral nerve (FN) and obturator nerve (ON), ischiatic tuberosity (IT), greater trochanter of the femur (GT) and the sciatic nerve (SN) indicated. © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia 345 and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. Table 1 Block conﬁdence score used for the guided saline (GSB; 10 dogs), guided bupivacaine (GBB; 10 dogs) and blind bupivacaine (GBB) groups. Scale of 1 (poor) to 4 (high) conﬁdence scoring that the block will be successful for guided (ultrasound and peripheral nerve locator) and blind techniques, respectively. The score was performed immediately post block prior to surgery. Subjective score Description Guided 1 Not conﬁdent at all, no conﬁdence of needle in correct position 2 Poor conﬁdence, appropriate response with peripheral nerve locator (PNL), but not conﬁrmed with ultrasound 3 Fairly conﬁdent, PNL response, correct anatomical location but no doughnut sign 4 Very conﬁdent, PNL response, visualization of doughnut sign Blind 1 Not conﬁdent at all, cannot properly identify anatomical landmarks 2 Poor conﬁdence, unsure of facial plane 3 Fairly conﬁdent 4 Very conﬁdent, nerve response observed Modiﬁed from Gray et al. (2019) © Copyright 2019 with permission of the Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia. dampening of invasive BP system. An isotonic crystalloid 0.1 mg kge1 for 5 days. Furthermore, dogs assigned to the GSB (lactated Ringer’s solution; Fresenius Kabi) was administered group were administered US-guided nerve blocks (0.1 mL kge1 at 5 mL kge1 houre1 for the duration of anaesthesia. The ﬁrst bupivacaine 5 mg mLe1 per site) of the medial saphenous and surgical incision was planned for 60 minutes after the blocks lateral proximal sciatic nerves (Costa-Farre et al. 2011) at the were performed. end of surgery prior to recovery. In dogs where the anaesthetist deemed the response to Intraoperative monitoring surgical stimulation as severe (tachycardia, tachypnoea, rapidly lightened plane of anaesthesia), rescue analgesic drugs Physiological variables were monitored with a Primus (Dr€ ager, were administered without delay. The rescue protocol con- RSA) anaesthetic workstation and multiparameter physiologic sisted of transiently increasing the FE0 Iso to 1.8%e2.0%, monitor (Inﬁnity Delta XL; Dr€ager) by an experienced anaes- administering a single intramuscular dose of ketamine 1 mg thetist (blinded investigator). During the surgical procedure, fR, kge1 and a constant rate infusion of fentanyl 0.005 mg kge1 HR, invasive SAP, MAP and DAP, oesophageal temperature houre1 intraoperatively and postoperatively for 24 hours. (T) and FE0 Iso were monitored continuously but recorded at standardized time points relevant to this study. The study time Data analysis points were 1 minute before, at the time of (0 minutes) and 1, 2, 4, 5, 6, 8, 10, 15, 20 and 25 minutes after the skin incision Physiological variables recorded at the time of the second event (ﬁrst surgical event). In addition, event notes were made on the (arthrotomy) and up to two time points after were included. datasheet when the joint was opened and distended (arthrot- Data at these time points were examined and the highest omy; second surgical event), using a stiﬂe extractor for at least values for the majority of variables within that time point were 2 minutes. A binomial subjective score was assigned by the taken as a response to surgical stimulus. If there was no anaesthetist who was unaware of the allocated group as ‘Yes’ change in the variables, then the values at the time of the event if there was a response to surgical stimulation or ‘No’ if there were used. Data distribution was assessed by inspecting was no discernible response at each time point. Criteria for a descriptive statistics, histograms plots and the Ander- response to surgical stimulation (Yes) was movement, a soneDarling test for normality. lightened plane of anaesthesia or an increase (>25%) in the measured physiological variable values. Part A A binomial classiﬁcation was used where dogs were expected Intraoperative analgesia and rescue interventions to either respond (Yes; GSB) or not respond (No; GBB) to sur- Morphine [0.3 mg kge1; Morphine, 10 mg mLe1; Pharma-Q gical stimulation. This binomial classiﬁcation was applied to Holdings (Pty) Ltd.] was administered to all dogs intra- receiver operator characteristic (ROC) curves comparing the operatively every 2 hours and postoperatively every 4 hours for actual value and the change in the physiological variables 24 hours. Meloxicam (5 mg mLe1, Metacam; Boehringer between GSB and GBB at the arthrotomy event. The change in Ingelheim, RSA) 0.2 mg kge1 was administered subcutane- value of a variable (D value) was calculated by subtracting the ously 1 hour prior to induction followed by a daily oral dose of value at the event from the value recorded 1 minute before 346 © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. start of surgery. The prevalence of the response to surgery was detecting a response to surgical stimulus. The highest speci- set to 50%. The Youden index (J) and associated criterion for ﬁcity was that of SAP. However, the disproportion in sensitivity each variable was used as the objective cut-off point between (60%) and speciﬁcity (95%) made SAP a poor indicator on its response (indicating block failure) and no response to surgical own. The highest sensitivity was that of DMAP. However, the stimulation. In addition, sensitivity, speciﬁcity, positive and disproportion in sensitivity (100%) and speciﬁcity (60%) made negative likelihood ratios, and positive and negative predictive DMAP a poor indicator on its own. values for the detection of nerve block failure were calculated from criterion values. Part B There was an association between the subjective and objective Part B scores with DHR or SAP only (Fig. 2). There was no difference The associated criterion for each variable (determined in part between objective and subjective scores for DHR or SAP. There A) was used as an objective score to detect a response to sur- was no agreement for DfR, slight agreement for HR, DSAP, gical stimulation in the BBB group (10 dogs). The agreement DMAP and fR, fair agreement for MAP, DAP and DDAP, between the objective score and the binomial subjective score moderate agreement for DHR and substantial agreement for for each variable in the BBB group was assessed by means of SAP with the subjective score. The strength and direction of 2 2 contingency tables. Fisher's exact test (determine asso- the association (Kendall tau-b) of the objective score with each ciation), McNemar’s test (determine differences) and Cohen’s conﬁdence score is shown in Fig. 3. BP variables and their kappa (assess inter-score reliability) values were calculated. effectiveness in objective detection of nerve block failure are The Kendall tau-b rank correlation coefﬁcient was used to presented in Table 3. assess the agreement between the binomial subjective and objective score for each of the assigned conﬁdence scores. Discussion Data were presented as mean ± standard deviation. Data In this study, dogs in the GSB group that were surgically analyses were performed using commercially available statis- stimulated during a surgical plane of anaesthesia demon- tical software (Minitab version 18; Minitab Ltd. LLC; PA, USA strated a detectable response to arthrotomy. The cardiovas- and MedCalc Statistical Software version 20.211; MedCalc cular variables, unlike the respiratory variables, showed good Software, Belgium). Fisher’s exact, McNemar and Kendall tau- diagnostic ability to detect nociception. We propose the use of b p values of 6 mmHg), DSAP (>10 mmHg) or DDAP (>8 mmHg) values were assessed as: no (0), slight (0.01e0.20), fair as cut-off values for the objective detection of nerve block (0.21e0.40), moderate (0.41e0.60), substantial (0.61e0.80) failure in dogs undergoing arthrotomy. There was a poor as- and perfect (0.81e1.00) agreement. sociation between nerve block conﬁdence scoring and the outcome of the block based on subjective and objective scores. Results Nurse anaesthetists, practising in human medicine, specu- lated that a degree of overlap existed in physiological variables A sample of 14 male (40.8 ± 12 kg body weight; 5 ± 1 out of 9 used for the intraoperative assessment of a response to surgical body condition; 4.4 ± 2.6 years old) and 16 female (34.3 ± stimulation and anaesthetic depth (Stomberg et al. 2001). 11.4 kg body weight; 6 ± 2 out of 9 body condition; 4.6 ± 2.5 However, cardiovascular variables (HR and BP) and ventila- years old) dogs were included in the study. All dogs completed tory variables (fR and VT) had better association with a the study, none of the responses to surgical stimulus were se- response to surgical stimulation (i.e. nociception) compared vere and therefore none of the dogs required rescue analgesic with the assessment of anaesthetic depth (Stomberg et al. intervention. Anaesthetic times were 116.5 ± 37.4 minutes for 2001). However, an inadequate plane of anaesthesia can premedication to arthrotomy and 71.3 ± 24.4 minutes for make the distinction between nociception and arousal difﬁcult block to arthrotomy. to determine. The minimum alveolar concentration (MAC) of isoﬂurane in the dog is 1.28% (Steffey & Howland 1977). A Part A MAC multiple of 1.2e1.4 (FE0 Iso of 1.54%e79%) is required to The results for the ROC analysis indicated that cardiovascular inhibit movement in response to a noxious stimulus in 95% of variables had a good and respiratory variables had a poor anaesthetized humans (De Jong & Eger 1975; Aranake et al. discriminating ability in distinguishing a response to surgical 2013). The current study was not a MAC ﬁnding study and stimulus (Table 2). all dogs were maintained at a clinically relevant FE0 Iso of 1.6 ± Evaluation of J indicated that HR, DHR, fR and DfR did not 0.06%. In human medicine, isoﬂurane at a concentration of meet the empirical benchmark (i.e. J > 0.5) for diagnostic 1.5 times MAC did not prevent a haemodynamic response to purposes. The J for MAP and DAP were the most effective for noxious stimuli (Inada et al. 1997). Similarly, in our study, © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia 347 and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. Table 2 Summary of the receiver operator characteristic (ROC) analysis of guided saline block (GSB; 10 dogs; response to surgical stimulus) and guided bupivacaine block (GBB; 10 dogs; no response to surgical stimulus) indicating the maximum potential effectiveness of heart rate (HR), DHR, respiratory rate (fR), DfR, systolic arterial pressure (SAP), DSAP, mean arterial pressure (MAP), DMAP, diastolic arterial pressure (DAP) and DDAP in detecting a response to surgical stimulus (stiﬂe arthrotomy). All dogs were premedicated with medetomidine 0.01 mg kge1 and morphine 0.3 mg kge1 injected intramuscularly, anaesthesia was induced with propofol and maintained with isoﬂurane (FE0 Iso 1.6%) in oxygen. ROC AUC ROC 95% CI p Z J J 95% CI AC AC 95% CI SE (%) SP (%) PPV NPV PLR NLR HR 0.75 0.59e0.88 0.0023 3.05 0.5 0.22e0.65 >77 67e83 80 70 72.7 77.8 2.67 0.29 DHR 0.76 0.6e0.88 0.0007 3.39 0.45 0.2e0.65 >1 e2 to 10 55 90 84.6 66.7 5.5 0.5 fR 0.57 0.4e0.72 0.46 0.73 0.2 0.1e0.35 >10 6e13 40 80 66.7 57.1 2 0.75 Df R 0.5 0.34e0.66 0.98 0.03 0.15 0.1e0.2 >e1 e4e3 65 20 44.8 36.4 0.81 1.75 SAP 0.82 0.66e0.92 127 123e135 60 95 92.3 70.4 12 0.42 DSAP 0.8 0.64e0.91 0.0001 3.81 0.6 0.35e0.75 >10 2e19 95 65 73.1 92.9 2.71 0.08 MAP 0.89 0.76e0.97 80 74e84 90 80 81.8 88.9 4.5 0.13 DMAP 0.8 0,69e0.94 6 1e12 100 60 71.4 100 2.5 0.00 DAP 0.93 0.8e0.99 73 68e78 85 90 89.5 85.7 8.5 0.17 DDAP 0.86 0.72e0.95 8 2e21 95 70 76.0 93.3 3.17 0.07 AC, associated criterion; AUC, area under the curve; CI, conﬁdence interval; J, Youden index; NLR, negative likelihood ratio; NPV, negative predictive value; p, signiﬁcance level; PLR, positive likelihood ratio; positive predictive value; SE, sensitivity; SP, speciﬁcity; Z, Z-score. where dogs were anaesthetized at 1.25 times MAC, there was a values are better suited for detecting a response to surgical detectable haemodynamic response to surgical stimulation in stimulation. Furthermore, based on negative predictive values, the GSB group when compared with the GBB group. we speculate that the DBP variables would have fewer false Ward et al. (2018) suggested an overconﬁdence in the suc- negatives associated with their use. However, the DBP vari- cess of peripheral nerve block techniques leading to a biased ables lack speciﬁcity (70%). Based on the positive predictive subjective assessment of the response to a surgical stimulus. values, we speculate that DBP variables might have false Furthermore, intraoperative subjective assessment of a response positives associated with their use. Thought should be given to to surgical stimulation in humans is reliant on a change in the relevance of false-positive nerve block failures in veterinary cardiovascular and respiratory variables (Stomberg et al. 2001). anaesthesia and its effect on ERAS (Campoy 2022). Unnec- This can explain why our subjective score was similar to the essary analgesic interventions (polypharmacy), owing to a objective scores for DHR and SAP for the detection of nerve high proportion of false positives, could result in longer periods block failure. However, the clinical application of using the cut- of sedation, increased time to ambulation, increased time to off values for HR (>77 beats minutee1 and DHR (>1 beat intake of oral solids and ﬂuids and therefore an increased minutee1) to deﬁne a response to surgical stimulation is duration of hospital stay. impractical. HR of 77 beats minutee1 or greater overlaps with There is a major limitation regarding the use of recommended the expected HR range for anaesthetized dogs and a change of 1 BP variables. Consideration should be given to the availability beat minutee1 is too small a ﬂuctuation to arouse any concern and accuracy of BP monitoring equipment. We speculate that the (Redondo et al. 2007). In some of the dogs in the GSB group, a use of oscillometric BP measurement is more conventional than decrease in HR was evident. The decrease in HR occurred invasive BP measurement for orthopaedic surgery in otherwise concurrently with a substantial increase in DAP and was most healthy animals. The degree of agreement required between likely as a result of an arterial baroreceptor reﬂex. The use of invasive arterial BP and veterinary-speciﬁc oscillometric devices SAP to detect a response to surgical stimulus was inadequate. is wide. According to the American College of Veterinary Internal The use of the absolute associated criterion values of the Medicine (ACVIM) consensus statement for dogs and cats (Brown cardiovascular variables in this study might not be directly et al. 2007), 50% of oscillometric measurements should be translatable to every dog undergoing a surgical procedure and within 10 mmHg or 80% of their measurements within 20 general anaesthesia. The cardiovascular effects of isoﬂurane mmHg of invasive pressure readings (SAP, DAP). These ranges and medetomidine and the antinociceptive effect of medeto- are larger than those proposed for our DBP variables, and we midine and morphine most likely had an unquantiﬁable in- therefore hesitate to recommend use of an oscillometric device in ﬂuence on the associated criterion values. It is important to the detection of a response to surgical stimulus. consider the effect of the different anaesthetic drug combina- We anticipated that the BBB group would have a larger tions administered and the cardiovascular system function of proportion of block failure associated with its use than the GBB the dog. Therefore, the authors speculate that using DBP group. Therefore, the BBB group was used to assess and 348 © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. Figure 2 Summary of comparison of subjective (left column) and objective (middle and right columns) assessment of nerve block outcome for blind bupivacaine block (BBB; 10 dogs). Criteria for objective assessment indicated in Table 2. Criteria for subjective assessment was movement, a lightened plane of anaesthesia or an increase (>25%) in the measured physiological variable values. Number of dogs (count) indicated. Proportions of block failure (black histogram) and block success (shaded histogram) shown. Values for Fisher’s exact t test, McNemar’s test and Cohen’s kappa coefﬁcient indicated. © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia 349 and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. Figure 3 Summary of nerve block outcome (fail or success) for blind bupivacaine block (BBB; 10 dogs). Subjective score (left column) compared with objective scores (middle and right columns) after being stratiﬁed into the assigned conﬁdence scores (2, 3 and 4) compared using Kendall tau- b rank correlation coefﬁcient. Proportions of block failure (black histogram) and block success (shaded histogram) shown. Number of dogs (count) indicated. Criteria for objective assessment indicated in Table 2. Criteria for subjective assessment was movement, a lightened plane of anaesthesia or an increase (>25%) in the measured physiological variable values. Criteria for the conﬁdence score is indicated in Table 1. 350 © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. Table 3 Recommended variables for the detection of nerve block failure in dogs undergoing stiﬂe arthrotomy. All dogs were premedicated with medetomidine 0.01 mg kge1 and morphine 0.3 mg kge1 injected intramuscularly, anaesthesia was induced with propofol and main- tained with isoﬂurane (FE0 Iso 1.6%) in oxygen. Indicator Value (mmHg) SE (%) SP (%) PLR NLR SAP Weak >127 60 95 12 0.42 DSAP Strong >10 95 65 2.71 0.08 * MAP Strong >80 90 80 4.5 0.13 * DMAP Strong >6 100 60 2.5 0.00 * DAP Moderate >73 85 90 8.5 0.17 DDAP Strong >8 95 70 3.17 0.07 * Diastolic (DAP), mean (MAP) and systolic (SAP) arterial pressure. * Suggested for use in the detection of nerve block failure. NLR, negative likelihood ratio; PLR, positive likelihood ratio; SE, sensitivity; SP, speciﬁcity. compare the performance of subjective and objective measures injecting and the needle tip was repositioned if there was for detecting nerve block failure. The failure rate of blind nerve resistance to injection. Upon critical evaluation of this study block techniques is highly variable with a range of 42.9% to based on the Declaration of Helsinki (DOH), we feel that the 85% (Thomson et al. 2021; Van der Laan et al. 2021; inclusion of the saline block did not adversely affect any of our Podsiedlik et al. 2022). The high variability is probably because dogs. The shortfall of this study with regards to the DOH was of the interplay of factors such as the complexity of the block, that the saline block did not provide any direct health beneﬁts body condition score of the animal (ease of structural palpa- (Ashall et al. 2023). Although the study will beneﬁt future tion) and the operator (skill, familiarity and anatomical canine patients, and we feel that it was ethical best practice, it knowledge). Therefore, the expected BBB failure rate was in is debatable and open for criticism based on the shortfall. better agreement with the DBP variables (60% to 70%) than The study had some notable limitations, especially because with the subjective scoring (20%). The success rate of PNL- the recommended variables were derived from an otherwise guided femoral and sciatic nerve blocks in dogs is between healthy dog population undergoing surgery using a stan- 76% and 86 % (Vettorato et al. 2012; Portela et al. 2013). dardized anaesthetic protocol. The effect of different pain states, Vettorato et al. (2012) used intraoperative fentanyl require- MAC multiples, anaesthetic drug combinations (anti- ment to qualify nerve block success. Portela et al. (2013) used nociceptive and cardiovascular effects) and physiological states the downward titration of FE0 Iso and the concurrent cardio- (especially cardiovascular function) on the associated criterion vascular response (>25% increase of HR or MAP) to determine values for the cardiovascular variables remains to be deter- success rate. The possibility of nerve block failure within the mined. An opportunity exists for further improvement of this GBB group cannot be excluded. Therefore, criterion values study, especially with regards to the values of the associated should be interpreted with caution. criterion in larger canine populations. This study will hopefully Serious complications (nerve injury, systemic toxicity) with enable other clinicians to develop an objective tool with peripheral nerve blocks are extremely rare. A prospective study pertinent criterion values for the detection of peripheral nerve of 7000 nerve blocks performed in humans indicated the block failure. prevalence of nerve injury and systemic toxicity as 0.0004% and 0.0001%, respectively (Barrington et al. 2009). There was Conclusion an inherent degree of risk associated with the techniques used The use of DBP variables should be considered as an objective in all three groups. According to the proposed serious harm score to detect a response to surgical stimulation and therefore and morbidity (SHAM) score by McGuirk et al. (2011), the nerve block failure. The determination of criterion values in score for the use of a placebo and blind group in the current different canine populations may help to evaluate the success study was 3 (moderate risk). McGuirk et al. (2011) questioned of nerve block techniques, thereby improving ERAS. the use of placebo treatments in peripheral nerve block studies. However, placebo groups still play an important role in pe- Acknowledgements ripheral nerve block studies (Papadopoulos et al. 2022). The BBB group had a higher degree of risk associated for nerve The authors thank Valley Farm Animal Hospital for their injury and block failure. To reduce the incidence of serious ﬁnancial support towards the study. The authors also thank complication, a good standard of practice was maintained in all Lomaen Medical (South Africa) for supplying the ultrasound three groups. Excessive tissue probing was avoided during machine and DIAG (South Africa) for supplying nerve stimu- needle tip positioning, aspirations were performed prior to lator needles for the project. © 2024 The Authors. Published by Elsevier Ltd on behalf of Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia 351 and Analgesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)., 51, 343e353 Detecting peripheral nerve block failure EP Basson et al. Authors' contributions Gray TR, Dzikiti BT, Zeiler GE (2019) Effects of hyaluronidase on ropivacaine or bupivacaine regional anaesthesia of the canine EPB and GEZ: study design, data collection, data management, pelvic limb. Vet Anaesth Analg 46, 214e225. data interpretation and preparation of the manuscript. AK: Haga HA, Dolvik N (2005) Electroencephalographic and cardio- study design, data collection, data interpretation and prepa- vascular variables as nociceptive indicators in isoﬂurane- ration of the manuscript. CB: study design, data collection, data anesthetized horses. Vet Anaesth Analg 32, 128e135. management and preparation of the manuscript. 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