Extravascular injection of neuromuscular blocking drugs: A systematic review of current evidence and management.

Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.

Serum concentrations of local anesthetics after unilateral interpectoral-pectoserratus plane block in breast cancer surgery: a pharmacokinetic study.

INTRODUCTION: The ultrasound-guided interpectoral-pectoserratus plane block is a fascial plane block for superficial surgery of the anterolateral chest wall. This technique involves injecting a relatively large volume of local anesthetics (typically 30 mL of 0.25%-0.50%, ie, 75-150 mg ropivacaine) underneath the major and minor pectoral muscles of the anterior thoracic wall. There is a potential risk of toxic serum concentrations of local anesthetics due to systemic absorption. METHODS: 22 patients scheduled for elective unilateral breast cancer surgery were included in this study. All surgery was performed with general anesthesia and an ultrasound-guided interpectoral-pectoserratus plane block with 2.5 mg/kg ropivacaine. Ten venous blood samples were collected at 0 (two samples) 10, 20, 30, 45, 60, 90 and 120 min and at 4 hours after performing the block. Free and total ropivacaine levels were measured at each time point. Albumin and alpha-1-acid-glycoprotein were measured to monitor shifts between the free and bound fraction of ropivacaine. RESULTS: Samples of 20 patients were analyzed. The mean dose of ropivacaine was 172.8 (22.5) mg. In 50% of the patients, the potentially toxic threshold of 0.15 µg/mL free ropivacaine concentration was exceeded. Mean peak serum concentration occurred at 20 min postinjection. CONCLUSIONS: This pharmacokinetic study demonstrated that a 2.5 mg/kg ropivacaine interpectoral-pectoserratus plane block may result in exceeding the threshold for local anesthetic systemic toxicity.

Timing of blood sampling for butyrylcholinesterase phenotyping in patients with prolonged neuromuscular block after mivacurium or suxamethonium.

INTRODUCTION: Variants of butyrylcholinesterase are frequently associated with prolonged response to suxamethonium or mivacurium. Butyrylcholinesterase (BChE) can be characterized by phenotyping and determination of genotype. Inappropriate timing of blood sampling might interfere with phenotyping methods. However, guidelines regarding delay between exposure to anaesthesia and testing are not clearly defined. In this study, the BChE activity and phenotype in an early (T1) and late (T2) phase were compared and the phenotype/genotype correlation was assessed. METHODS: Patients with a prolonged paralysis after mivacurium or suxamethonium were selected after ethical committee approval and written consent. BChE activity was based on butyrylthiocholine hydrolysis rate and phenotyping on differential inhibition of BChE activity with dibucaine and fluoride. DNA sequencing allowed genotypic characterization. RESULTS: We included the results of 20 patients with prolonged neuromuscular block (NMB) induced by mivacurium or suxamethonium. In these patients, BChE activity was different at T1 and T2 (2120 [1506-2733] U L-1 and 4055 [2810-5301] U L-1 , respectively; P = 0.0014; values are mean [95% CI]). When phenotyping was possible, phenotyping at T1 and T2 yielded identical results. Phenotyping failed to identify one new variant (p.Tyr146Cys) and the K variant in 14 of 16 patients. CONCLUSION: Anaesthesia interfered with BChE activity, but not with phenotyping. Phenotyping can be performed on blood drawn during or immediately after recovery of mivacurium or suxamethonium to screen for clinically relevant variants of BChE. However, accurate diagnosis of BChE deficiency needs further confirmation by determination of genotype.

Supra-inguinal injection for fascia iliaca compartment block results in more consistent spread towards the lumbar plexus than an infra-inguinal injection: a volunteer study.

BACKGROUND AND OBJECTIVES: Lumbar plexus block has been used to provide postoperative analgesia after lower limb surgery. The fascia iliaca compartment block (FICB) has been proposed as an anterior approach of the lumbar plexus targeting the femoral, obturator and lateral femoral cutaneous nerve. However, both radiological and clinical evidence demonstrated that an infra-inguinal approach to the fascia iliaca compartment does not reliably block the three target nerves.We hypothesized that a supra-inguinal approach of the fascia iliaca compartment results in a more consistent block of the three target nerves than an infra-inguinal approach. METHODS: We performed a randomized controlled, double-blind trial in 10 healthy volunteers. Both an infra-inguinal FICB (I-FICB) and a supra-inguinal FICB (S-FICB) were performed on the left or the right side in each volunteer. Forty milliliters of lidocaine 0.5% was injected with each approach. Sensory and motor block and spread of local anesthetics (LA) on MRI were assessed. RESULTS: After an S-FICB, 80% of the volunteers had a complete sensory block of the medial, anterior and lateral region of the thigh, compared with 30% after an I-FICB (p=0.035). There was an insignificant effect on motor function with both approaches. After an S-FICB, in 8 out of 10 volunteers there was spread of LA in the expected anatomic location of the obturator nerve on MRI compared with 1 out of 10 volunteers after an I-FICB (p=0.0017). The cranial spread of LA after an S-FICB on MRI was higher than after an I-FICB (p=0.007), whereas there was a more caudal spread of LA on MRI after an I-FICB than after an S-FICB (p=0.005). CONCLUSIONS: An S-FICB produces a more complete sensory block of the medial, anterior and lateral region of the thigh, compared with an I-FICB. Our study demonstrates that an S-FICB with 40 mL of LA more reliably spreads LA to the anatomical location of the three target nerves of the lumbar plexus on MRI than an I-FICB. An S-FICB also leads to a more consistent spread in a cranial direction under the fascia iliaca and around the psoas muscle. CLINICAL TRIAL REGISTRATION: This work was registered with the European clinical trial registry: Identifier Eudra CT 2015-004607-24.

Opening Injection Pressure Is Higher in Intraneural Compared With Perineural Injections During Simulated Nerve Blocks of the Lower Limb in Fresh Human Cadavers.

BACKGROUND AND OBJECTIVES: Needle-induced nerve trauma and intraneural injection can lead to neurologic injury during peripheral nerve blocks. In this study, we assessed the utility of opening injection pressure (OIP), time to OIP, and rate of rise to OIP in detecting needle-nerve contact and intraneural injection. METHODS: Five common ultrasound-guided blocks of the femoral, saphenous, subgluteal sciatic, tibial, and common peroneal nerves were simulated in 10 fresh cadavers. Opening injection pressure was defined as peak psi in the 60-second interval during which the injection is initiated. Pressure-time curves were constructed separately for intraneural and perineural injections for each of the 5 nerves studied. RESULTS: Opening injection pressure was higher for intraneural than for perineural injections (P < 0.001), ranging from 21.5 psi (1111.9 mm Hg) to 25.8 psi (1334.2 mm Hg) for intraneural injections and from 3.8 psi (196.5 mm Hg) to 6.1 psi (315.5 mm Hg) for perineural injections. Time to OIP tended to be shorter for intraneural than for perineural injections, particularly for the subgluteal sciatic, tibial, and common peroneal nerves. Curves of intraneural injections had steep slopes with high peaks; curves of perineural injections had low slopes followed by plateaus. Rise to OIP was greater for intraneural than for perineural injections. CONCLUSIONS: In our fresh human cadaver model, OIP detected intraneural needle placement. Monitoring of OIP could be useful in detecting and/or preventing intraneural injection during nerve blocks in the clinical setting.

A Longitudinal Supra-Inguinal Fascia Iliaca Compartment Block Reduces Morphine Consumption After Total Hip Arthroplasty.

BACKGROUND AND OBJECTIVES: The role of a fascia iliaca compartment block (FICB) for postoperative analgesia after total hip arthroplasty (THA) remains questionable. High-dose local anesthetics and a proximal injection site may be essential for successful analgesia. High-dose local anesthetics may pose a risk for local anesthetic systemic toxicity. We hypothesized that a high-dose longitudinal supra-inguinal FICB is safe and decreases postoperative morphine consumption after anterior approach THA. METHODS: We conducted a prospective, double blind, randomized controlled trial. Patients scheduled for THA were randomized to group FICB (longitudinal supra-inguinal FICB with 40-mL ropivacaine 0.5%) or group C (control, no block). Standard hypothesis tests (t test or Mann-Whitney U test, χ test) were performed to analyze baseline characteristics and outcome parameters. The primary end point of the study was total morphine (mg) consumption at 24 hours postoperatively. Serial total and free ropivacaine serum levels were determined in 10 patients. RESULTS: After obtaining ethical committee approval and written informed consent, 88 patients were included. Mean (SD) morphine consumption at 24 hours postoperatively was reduced in group FICB compared to group C: 10.25 (1.64) mg versus 19.0 (2.4) mg (P = 0.004). Using a mean dose of 2.6-mg/kg ropivacaine (range, 2-3.4 mg/kg), none of the patients had total or free ropivacaine levels above the maximum tolerated serum concentration. CONCLUSIONS: We conclude that a high-dose longitudinal supra-inguinal FICB reduces postoperative morphine requirements after anterior approach THA.Clinical Trials Registry: EU Clinical Trials Register. www.clinicaltrialsregister.eu #2014-002122-12.

A double-blind randomized controlled trial comparing dexamethasone and clonidine as adjuvants to a ropivacaine sciatic popliteal block for foot surgery.

BACKGROUND AND AIMS: A popliteal block is effective in managing postoperative pain for foot surgery, but since the duration of analgesia is limited following a single-shot popliteal fossa block technique, methods to prolong effective postoperative analgesia are mandatory. The aim of this study was to assess the effect of adjuvants to ropivacaine on the duration of sensory and motor block. METHODS: In this double-blind randomized placebo-controlled study, we evaluated the analgesic effect of clonidine or dexamethasone (DXM) when added to ropivacaine for hallux valgus surgery. After obtaining institutional ethics research board approval and written informed consent, a total of 72 patients were randomly allocated. Fifty-seven of these patients were statistically analyzed. All patients received an ultrasound-guided single-shot popliteal fossa block with 30 mL of ropivacaine 0.75%, supplemented with saline, clonidine 100 µg, or DXM 5 mg. The primary end point was time to first pain sensation. Secondary end points were time to complete sensory and motor block regression. RESULTS: Compared to saline, duration to first pain sensation was prolonged by 9 hours (mean ± standard deviation: 31±9 hours) (42%) in the DXM group (P=0.024) and by 6 hours (28±10 hours) (27%) in the clonidine group (P=0.024). Compared to saline, DXM prolonged both complete sensory and motor blockade by 12 hours (25±7 hours) (46%) and 13 hours (36±6 hours) (55%), respectively, while clonidine prolonged complete sensory and motor blockade by 7 hours (30±7 hours) (27%) and 2 hours (22±5 hours) (10%), respectively. DXM prolonged sensory block regression time by 6 hours (21±7 hours) (41%) and clonidine by 2 hours (17±6 hours) (13%) compared to the control group (P=0.006). Similarly, DXM prolonged motor block regression by 7 hours (25±7 hours) (46%) and clonidine by 4 hours (21±4 hours) (19%) (P<0.0001). CONCLUSION: Addition of DXM and clonidine to ropivacaine significantly prolonged the duration of postoperative sensory and motor block.

Phrenic Nerve Injury After Radiofrequency Denervation of the Cervical Medial Branches.

Radiofrequency denervation of the cervical medial branches is a possible treatment for chronic cervical facet pain syndrome when conservative management has failed. According to the literature, complications after radiofrequency denervation of the cervical medial branches are rare. We report a case of possible phrenic nerve injury after ipsilateral radiofrequency denervation of the cervical medial branches following a posterolateral approach.

Full neurological recovery after extreme hypoglycemia during intensive insulin therapy: a case report.

Since 2000, there has been an ongoing debate regarding tightness of glycemic control in critically ill patients. An increased risk of hypoglycemia is observed in patients treated with an intensive insulin protocol targeting "normoglycemia," probably accounting for a reduction of the overall benefit. Hypoglycemia is associated with neurological side effects and is found to be an independent predictor of mortality in most trials; however, long-term sequelae are rare if glucose is administered early. We describe a case of prolonged, extreme hypoglycemia in a critically ill patient treated according to an intensive insulin protocol who recovered without any neurological deficit at discharge.

Hypoglycemia caused by siphoning of an insulin infusion.

STUDY OBJECTIVE: To determine--through reconstruction of a clinical situation in which a syringe filled with insulin was removed from the syringe pump, placed above the patient, then emptied into the patient--the different physical forces at work, and to examine the height of the syringe (and thus the hydrostatic force) necessary to move the plunger. DESIGN: Prospective study. SETTING: Research laboratory of a university. MEASUREMENTS: The clinical situation was simulated using eight 50-mL and eight 20-mL syringes. A pressure transducer, placed between the syringe and the extension tubing, measured the pressure difference over the extension tubing. The Poiseuille equation of the viscous resistance was used to calculate flow. MAIN RESULTS: The mean height needed for initiation of flow in the 50-mL syringes was 76 cm (range, 60-90 cm). In the 20-mL syringes, no flow could be generated up to heights of 200 cm. There was a large variability in the height and time required to generate flow in apparently identical syringes, probably due to differences in the static sticking of the plunger to the barrel. CONCLUSIONS: Studies testing the effect of siphoning using one syringe cannot be interpreted reliably. Smaller syringes are safer to avoid siphoning.

Levobupivacaine-sufentanil with or without epinephrine during epidural labor analgesia.

In a prospective, randomized, double-blind study, we investigated whether epinephrine increased the efficacy of levobupivacaine and sufentanil during epidural labor analgesia. Seventy term parturients received an epidural injection of levobupivacaine 0.125% and sufentanil 0.75 microg/mL with or without 1:800,000 epinephrine. After an initial dose of 10 mL, a patient-controlled analgesia pump was started. Total and hourly drug consumption, pain scores using the visual analog scale, sensory and motor block, duration of labor, vital variables, maternal and neonatal outcome, and side effects were compared. If the parturients experienced insufficient pain relief during the study, even after a rescue dose of 10 mL, they were excluded from further study and received 10 mL of bupivacaine 0.125% and sufentanil 0.75 microg/mL with 1:800,000 epinephrine. Hourly drug consumption, rescue dosing, and pain scores at 15 min and 20 min were lower in the epinephrine group. The incidence of motor block and duration of the second stage of labor tended to be higher in the epinephrine group and were associated with lower Apgar scores at 1 and 5 min. These findings suggest that the addition of epinephrine intensifies the effects of epidural levobupivacaine and sufentanil but may cause more motor block.