Rocuronium-induced respiratory paralysis refractory to sugammadex in Charcot-Marie-Tooth disease.

PURPOSE: Prolonged postoperative neuromuscular respiratory paralysis after administration of a nondepolarizing neuromuscular blocking agent is a serious concern during anesthetic management of patients with Charcot-Marie-Tooth disease (CMTD). Some recent reports have described rocuronium use without respiratory paralysis in CMTD patients when sugammadex was used for its reversal. We report a case in which an induction dose of rocuronium caused a prolonged respiratory paralysis in a patient with undiagnosed type 1A CMTD (CMT1A). CLINICAL FEATURES: A 63-yr-old-male with an American Society of Anesthesiologists Physical Status score of III underwent a left hip arthroplasty under general anesthesia for osteoarthritis. Preoperative pulmonary function testing indicated a restrictive impairment. Anesthesia was induced with fentanyl, remifentanil, propofol, and 0.73 mg·kg-1 of rocuronium. The train-of-four (TOF) count was 0 for the 273-min duration of surgery. After repeated doses of sugammadex failed to recover the TOF count and spontaneous respirations, a total of 1,200 mg (17.3 mg·kg-1) of sugammadex, which was assumed to be a sufficient amount for capturing the residual rocuronium, was administered. Although the patient expressed that he was awake via eye blinking, he could not breathe. Thus, he was placed on mechanical ventilation for 18 hr after surgery. A postoperative neurology consultation revealed a delayed nerve conduction velocity of 20 m·sec-1 and a mutated duplication of the PMP22 gene; a diagnosis of CMT1A was made. CONCLUSIONS: Our case shows that rocuronium can cause a prolonged neuromuscular respiratory paralysis refractory to sugammadex in patients with CMT1A and impaired respiratory function. Our case may also indicate that restrictive pulmonary impairment and low nerve conduction velocity of 20 m·sec-1 are predictive factors that cause prolonged neuromuscular respiratory paralysis refractory to sugammadex in CMT1A.

RéSUMé: OBJECTIF: La paralysie respiratoire neuromusculaire postopératoire prolongée après l'administration d'un bloqueur neuromusculaire non dépolarisant est une préoccupation sérieuse lors de la prise en charge anesthésique des patients atteints de la maladie de Charcot-Marie-Tooth (CMT). Certains comptes rendus récents ont décrit l'utilisation de rocuronium sans paralysie respiratoire chez les patients atteints de CMT lorsque le sugammadex était utilisé pour le neutraliser. Nous rapportons un cas dans lequel une dose d'induction de rocuronium a provoqué une paralysie respiratoire prolongée chez un patient atteint de CMT de type 1A (CMT1A) non diagnostiquée. CARACTéRISTIQUES CLINIQUES: Un homme de 63 ans avec un score de statut physique III selon la classification de l'American Society of Anesthesiologists a bénéficié d'une arthroplastie de la hanche gauche sous anesthésie générale pour son ostéo-arthrite. Les tests préopératoires de la fonction pulmonaire ont indiqué un syndrome restrictif. L'anesthésie a été induite avec du fentanyl, du rémifentanil, du propofol et 0,73 mg·kg-1 de rocuronium. Le décompte du train-de-quatre (TdQ) était de 0 pour toute la durée de la chirurgie, soit 273 minutes. Après l'échec de doses répétées de sugammadex qui n'ont pas réussi à rétablir un TdQ normal ni la respiration spontanée, un total de 1200 mg (17,3 mg·kg-1) de sugammadex (une quantité qu'on a présumé suffisante pour neutraliser le rocuronium résiduel) a été administré. Bien que le patient ait exprimé qu'il était éveillé en clignant des yeux, il ne pouvait pas respirer. Il a donc été placé sous ventilation mécanique pendant 18 heures après l'opération. Une consultation postopératoire en neurologie a révélé une vitesse de conduction nerveuse retardée de 20 m·sec-1 et une duplication mutée du gène PMP22; un diagnostic de CMT1A a été posé. CONCLUSIONS: Notre cas montre que le rocuronium peut provoquer une paralysie respiratoire neuromusculaire prolongée réfractaire au sugammadex chez les patients atteints de CMT1A et d'une altération de la fonction respiratoire. Notre cas pourrait également indiquer qu'un syndrome restrictif pulmonaire et une faible vitesse de conduction nerveuse de 20 m·sec-1 constituent des facteurs prédictifs provoquant une paralysie respiratoire neuromusculaire prolongée réfractaire au sugammadex dans les cas de CMT1A.

Effects of Local Anesthetic Volume (Standard Versus Low) on Incidence of Hemidiaphragmatic Paralysis and Analgesic Quality for Ultrasound-Guided Superior Trunk Block After Arthroscopic Shoulder Surgery.

BACKGROUND: Relative to interscalene block, superior trunk block (STB) provides comparable analgesia and a reduced risk of hemidiaphragmatic paralysis. However, the incidence of hemidiaphragmatic paralysis remains high when a standard volume (15 mL) of local anesthetic is used. This study aimed to evaluate the effects of local anesthetic volume of STB on the incidence of phrenic nerve palsy, as well as its analgesic efficacy following arthroscopic shoulder surgery. METHODS: Patients scheduled for elective arthroscopic shoulder surgery were randomized to receive ultrasound-guided STB using either 5- or 15-mL 0.5% ropivacaine before general anesthesia. The primary outcome was the incidence of hemidiaphragmatic paralysis at 30 minutes after block. The secondary outcomes were pulmonary function, grade of sensory and motor blockade, pain score, opioid consumption, adverse effects, and satisfaction. RESULTS: Relative to standard-volume STB, low-volume STB was associated with a lower incidence of hemidiaphragmatic paralysis after block (14.3 [4.8%-30.3%] vs 65.7 [46.8%-80.9%]; difference 51.4% [95% confidence intervals {CIs}, 29.0%-67.1%]; P < .0001) and at the postanesthesia care unit (9.4% vs 50.0%; difference 40.6 [95% CI, 18.9%-57.7%]; P = .0004). Pulmonary function was also better preserved in the low-volume group than in the standard-volume group. The extent of the sensory and motor blocks was significantly different between the groups. Pain-related outcomes, satisfaction, and any adverse events were not significantly different between the groups. CONCLUSIONS: Low-volume STB provided a lower incidence of hemidiaphragmatic paralysis with no significant difference in analgesic efficacy relative to standard-volume STB for arthroscopic shoulder surgery.

[A woman with hypoxia after shoulder arthroscopy]. / Een vrouw met hypoxie na artroscopie van de schouder.

A 58-year-old female with a history of obesity, smoking and hypertension underwent shoulder arthroscopy. Prior to the arthroscopy, patient received an interscalene brachial plexus block. After the arthroscopy, patient had an oxygen saturation of 85%, caused by an unilateral diaphragm paralysis due to a phrenic nerve block.

Hemidiaphragmatic paralysis following ultrasound-guided anterior vs. posterior suprascapular nerve block: a double-blind, randomised control trial.

Interscalene brachial plexus block provides analgesia for shoulder surgery but is associated with hemidiaphragmatic paralysis. Before considering a combined suprascapular and axillary nerve block as an alternative to interscalene brachial plexus block, evaluation of the incidence of diaphragmatic dysfunction according to the approach to the suprascapular nerve is necessary. We randomly allocated 84 patients undergoing arthroscopic shoulder surgery to an anterior or a posterior approach to the suprascapular nerve block combined with an axillary nerve block using 10 ml ropivacaine 0.375% for each nerve. The primary outcome was the incidence of hemidiaphragmatic paralysis diagnosed by ultrasound. Secondary outcomes included: characterisation of the hemidiaphragmatic paralysis over time; numeric rating scale pain scores; oral morphine equivalent consumption; and patient satisfaction. The incidence of hemidiaphragmatic paralysis was 40% (n = 17) vs. 2% (n = 1) in the anterior and posterior groups, respectively (p < 0.001). In one third of patients with hemidiaphragmatic paralysis, it persisted beyond the eighth hour. The median (interquartile range [range]) oral morphine equivalent consumption was significantly higher in the posterior approach when compared with the anterior approach, whether in the recovery area (20 [5-31 (0-60)] mg vs. 7.5 [0-14 (0-52)] mg, respectively; p = 0.004) or during the first 24 h (82 [61-127 (12-360) mg] vs. 58 [30-86 (0-160)] mg, respectively; p = 0.01). Patient satisfaction was comparable between groups (p = 0.6). Compared with the anterior approach, diaphragmatic function is best preserved with the posterior needle approach to the suprascapular nerve block.

Botox injection into the lower esophageal sphincter induces hiatal paralysis and gastroesophageal reflux.

BACKGROUND: Endoscopic intrasphincteric injection of Botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that the ISIB reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm, surrounds the cranial half of the LES and works like an external LES. We studied the effects of ISIB on the LES and hiatal contraction and gastroesophageal reflux (GER). Fourteen patients treated with ISIB were studied. Esophageal manometry-impedance recordings were performed before and after the ISIB. Hiatal contraction was assessed during tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise. In 6 subjects, the manometry were repeated 6-12 mo after the ISIB. The esophagogastric junction (EGJ) pressure was measured at end expiration (LES pressure) and at the peak of maneuvers (hiatal contraction). Transdiaphragmatic pressure (pdi; force of diaphragmatic contraction) was measured at the peak of forced inspiration. GER was measured from the impedance recordings. The EGJ pressure at end expiration (LES pressure) decreased significantly after the Botox injection. The peak EGJ pressure at tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise was also dramatically reduced by the ISIB. There was no effect of Botox on the pdi during forced inspiration. Seven of 10 subjects demonstrated GER during maneuvers following the ISIB. Six to 12 mo after ISIB, the LES and hiatal contraction pressure returned to the pre-ISIB levels. ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER.NEW & NOTEWORTHY The sphincter mechanism at the lower end of the esophagus comprises smooth muscle lower esophageal sphincter (LES) and skeletal muscle crural diaphragm (hiatus). Current thinking is that the endoscopic intrasphincteric injection of Botox (ISIB), used routinely for the treatment of achalasia esophagus, reduces LES pressure. Our study shows that ISIB, even though injected into the LES, diffuses into the hiatus and causes its paralysis. These findings emphasize the importance of esophageal hiatus as an important component of the antireflux barrier and that the ISIB is refluxogenic.

Immune Checkpoint Inhibitor-Induced Myositis: a Case Report and Literature Review.

PURPOSE OF THE REVIEW: We clarify clinical characteristics of patients with immune checkpoint inhibitor (ICI)-induced myositis. RECENT FINDINGS: In 13 of 15 cases with ICI-induced myositis, the type of malignancy was melanoma. Eight, 4, and 3 patients received anti-PD-1 alone, anti-CTLA4 alone, and a combination of those, respectively. The mean period to the onset of ICI-induced myositis from the initiation of ICI was 4 weeks. Myocarditis was a complication in five patients. Seven of the patients died. The causes of death were myocarditis in three patients, respiratory muscle paralysis in two patients, and cancer progression in two patients. In patients without myocarditis or respiratory muscle paralysis, the prognosis for myositis was favorable with normalization of the CK levels occurring upon the cessation of ICI and the administration of immunosuppressive agents. Myocarditis and respiratory muscle paralysis are the major causes of death as immune-related adverse events in patients with ICI-induced myositis.

Conium maculatum intoxication: Literature review and case report on hemlock poisoning.

The aim of this paper is to highlight the symptomatology in three Conium maculatum intoxication incidents, one of which was fatal. A number of studies were reviewed in order to update and summarize the relevant literature on the incidence, sociodemographic variables, method of poisoning, pathophysiology, diagnosis, variables associated with survival and fatality, management, and treatment of C. maculatum intoxication as well as the biosynthesis and biological effects of poison hemlock alkaloids. Results show that hemlock poisoning is relatively rare, although incidence varies in different regions, despite its worldwide distribution. Hemlock poisoning is more common in European and especially Mediterranean countries. The majority of the patients are adult males over 38 years of age. The clinical course of hemlock poisoning includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, rhabdomyolysis, and acute renal failure. The therapeutic management focuses on absorption reduction, close observation for complications, and supportive therapy (especially for respiration). Acute occurrence is severe and life-threatening, but the survival rate is high if treatment is provided promptly. Recovery is rapid, generally taking only a few days.

Reduced Hemidiaphragmatic Paresis With a "Corner Pocket" Technique for Supraclavicular Brachial Plexus Block: Single-Center, Observer-Blinded, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Hemidiaphragmatic paresis is common after supraclavicular brachial plexus block (SCBPB). In this randomized trial, we compared the incidence of hemidiaphragmatic paresis in patients who had local anesthetic injected primarily in the corner pocket (defined as the intersection of the first rib and subclavian artery) during SCBPB with that of patients who underwent injection primarily inside the neural cluster. METHODS: Thirty-six patients scheduled for right elbow, forearm, wrist, or hand surgery under SCBPB (using 12.5 mL of 0.75% ropivacaine and 12.5 mL of 2% lidocaine with 1:200,000 epinephrine) were randomly assigned to 1 of 2 groups. In group CP, local anesthetic was injected primarily in the corner pocket (20 mL) and secondarily inside the neural cluster (5 mL). In group NC, local anesthetic was deposited primarily inside the neural cluster (20 mL) and secondarily in the corner pocket (5 mL). The primary outcome was the incidence of hemidiaphragmatic paresis, as measured by M-mode ultrasonography 30 minutes after SCBPB. RESULTS: The incidence of hemidiaphragmatic paresis was significantly lower in group CP than in group NC (27.8% vs 66.7%, P = 0.019). The median decreases in forced expiratory volume at 1 second (7.5% [interquartile range, 3.3%-17.1%] vs 24.4% [interquartile range, 10.2%-31.2%]; P = 0.010) and forced vital capacity (6.4% [interquartile range, 3.3%-11.1%] vs 19.3% [interquartile range, 13.7%-33.2%]; P = 0.001) were also lower in group CP than in group NC. CONCLUSIONS: The incidence of hemidiaphragmatic paresis was effectively reduced when local anesthetic was injected primarily in the corner pocket during right-sided SCBPB. However, the 28% incidence of hemidiaphragmatic paresis associated with the corner pocket technique may still represent a prohibitive risk for patients with preexisting pulmonary compromise. CLINICAL TRIAL REGISTRATION: This study was registered at Clinical Trial Registry of Korea, identifier KCT0001769.

3,4-diaminopyridine reverses paralysis in botulinum neurotoxin-intoxicated diaphragms through two functionally distinct mechanisms.

Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that prevent neurotransmitter release from peripheral nerve terminals by cleaving presynaptic proteins required for synaptic vesicle fusion. The ensuing neuromuscular paralysis causes death by asphyxiation. Although no antidotal treatments exist to block toxin activity within the nerve terminal, aminopyridine antagonists of voltage-gated potassium channels have been proposed as symptomatic treatments for botulism toxemia. However, clinical evaluation of aminopyridines as symptomatic treatments for botulism has been inconclusive, in part because mechanisms responsible for reversal of paralysis in BoNT-poisoned nerve terminals are not understood. Here we measured the effects of 3,4-diaminopyridine (DAP) on phrenic nerve-elicited diaphragm contraction and end-plate potentials at various times after intoxication with BoNT serotypes A, B, or E. We found that DAP-mediated increases in quantal content promote neurotransmission from intoxicated nerve terminals through two functionally distinguishable mechanisms. First, DAP increases the probability of neurotransmission at non-intoxicated release sites. This mechanism is serotype-independent, becomes less effective as nerve terminals become progressively impaired, and remains susceptible to ongoing intoxication. Second, DAP elicits persistent production of toxin-resistant endplate potentials from nerve terminals fully intoxicated by BoNT/A, but not serotypes B or E. Since this effect appears specific to BoNT/A intoxication, we propose that DAP treatment enables BoNT/A-cleaved SNAP-25 to productively engage in fusogenic release by increasing the opportunity for low-efficiency fusion events. These findings have important implications for DAP as a botulism therapeutic by defining conditions under which DAP may be clinically effective in reversing botulism symptoms.

Total spinal block after local anesthetic administration through the wrong access port of a spinal infusion pump. / Bloqueo espinal total tras administración de anestésico local por el puerto de acceso equivocado de una bomba de infusión intratecal.

We present a case reported on the SENSAR database. A patient with a spinal infusion pump was admitted for reservoir refill. On administration of 22ml of 0.75% bupivacaine the patient suffered a total spinal block with widespread loss strength and respiratory arrest. The patient required emergency orotracheal intubation, mechanical ventilation and admission to ICU, where extubation was achieved within two hours without incidences. At a later stage it was stated that the local anaesthetic had been administered via the access port for bolus or contrast administration instead of via the access to the reservoir. Analysis of the incident showed up latent factors related to absence lack of personnel training and internal protocols. The following measures were taken: pain unit meeting, alert sent to SENSAR bulletin and training request for members of the service.

Reduced hemidiaphragmatic paresis with extrafascial compared with conventional intrafascial tip placement for continuous interscalene brachial plexus block: a randomized, controlled, double-blind trial.

BACKGROUND.: The incidence of hemidiaphragmatic paresis with continuous interscalene brachial plexus block (CISB) can approach 100%. We tested the hypothesis that extrafascial placement of the catheter tip reduces the rate of hemidiaphragmatic paresis compared with intrafascial tip placement for CISB while providing effective analgesia. METHODS.: Seventy patients undergoing elective major shoulder surgery under general anaesthesia were randomized to receive an ultrasound-guided CISB plexus block for analgesia with the catheter tip placed either within (intrafascial group) or immediately outside (extrafascial group) the brachial plexus sheath midway between the levels of C5 and C6. Catheters were bolus dosed with ropivacaine 0.5% 20 ml before surgery, followed by an infusion of ropivacaine 0.2% at 4 ml h -1 for the first 2 days after surgery. The primary outcome was hemidiaphragmatic paresis measured by M-mode ultrasonography on postoperative day (POD) 1. Secondary outcomes included forced vital capacity, forced expiratory volume in 1 s, and rest pain scores. RESULTS.: The incidence of hemidiaphragmatic paresis on POD 1 was significantly reduced in the extrafascial group {intrafascial, 41% [95% confidence interval (CI) 25-59%]; extrafascial, 15% (95% CI 5-32%); P =0.01}. We were unable to detect a difference between groups in any of the functional respiratory outcomes or in rest pain scores [numerical rating scale (1-10): intrafascial, 3 (95% CI 2-3); extrafascial, 3 (95% CI: 2-4); P =0.93] on POD 1. CONCLUSIONS.: Placement of the catheter tip immediately outside of the brachial plexus sheath reduced the incidence of hemidiaphragmatic paresis on POD 1 associated with ultrasound-guided CISB while providing effective analgesia after major shoulder surgery. Our results do not support the routine placement of the catheter tip within the brachial plexus sheath for CISB. CLINICAL TRIAL REGISTRATION.: NCT02433561.

A comparison of ultrasound-guided interscalene and supraclavicular blocks for post-operative analgesia after shoulder surgery.

BACKGROUND: In contrast to interscalene block, there was little information regarding the analgesic efficacy of supraclavicular block for shoulder surgery. This study aimed to compare the analgesic efficacy and side effects of interscalene and supraclavicular blocks for shoulder surgery. METHODS: Patients scheduled for shoulder surgery were assigned to receive either ultrasound-guided interscalene (n = 25) or supraclavicular block (n = 24) with 20 ml of 0.375% ropivacaine. We assessed the duration of post-operative analgesia as a primary outcome and pain scores, supplemental analgesia, diaphragmatic excursion, motor block, fingertip numbness, side effects, and patient satisfaction as secondary outcomes. RESULTS: The duration of post-operative analgesia was not statistically different between groups: 868 (800-1440) min for supraclavicular block vs. 800 (731-922) min for interscalene block (median difference -85 min, 95% CI, -283 to 3 min, P = 0.095). The incidence of diaphragmatic paresis was significantly lower in the supraclavicular block group compared with that in the interscalene block group, both at 30 min after the block (66.7% vs. 92%, P = 0.021) and in the post-anaesthesia care unit (62.5% vs. 92%, P = 0.024). Motor block was higher in the supraclavicular block group in the post-anaesthesia care unit, however, not at 24 h. Other secondary outcomes were similar for both groups. CONCLUSIONS: This study showed no statistically significant difference in the duration of post-operative analgesia between the supraclavicular and interscalene blocks. However, the supraclavicular block was associated with a lower incidence of diaphragmatic paresis compared with that of the interscalene block after shoulder surgery.

[Progressive paralysis of the diaphragm following intra-abdominal chemotherapy]. / Paralysie diaphragmatique progressive consécutive à une chimiothérapie intra-abdominale.

INTRODUCTION: In patients presenting with intra-abdominal tumor and peritoneal carcinomatosis, cytoreductive surgery associated with hyperthermic chemotherapy may offer improved survival. We describe a case of diaphragmatic paralysis following that kind of procedure. CASE REPORT: A 60-year-old woman presented with respiratory insufficiency following cytoreductive surgery and intra-abdominal hyperthermic chemotherapy performed for pseudomyxoma intraperitonei. Pulmonary function assessment demonstrated a restrictive pattern. Three successive chest CT-scans demonstrated a thinning diaphragm muscle. Respiratory insufficiency eventually led to the death of our patient. CONCLUSION: We conclude in favor of a muscular degeneration of the diaphragm consecutive to the combined effect of cytoreductive surgery and intraperitoneal chemotherapy. Owing to the unusual nature of this complication, we did not consider it as a hypothesis at an early point in this patient's management. We think physicians should be aware of such a complication in order to consider it in a timely way. We recommend performing a biopsy of the diaphragm for pathology examination to assess muscular degeneration.

Effects of a fixed low-dose ropivacaine with different volume and concentrations on interscalene brachial plexus block: a randomized controlled trial.

BACKGROUND: Ultrasound guidance has reduced the amount of local anesthetics to achieve a successful block. Previous studies of the relationship between the volume or concentration of local anesthetics and the effects of the block were based on relatively high doses of local anesthetics. We tested the hypothesis that providing low dose of ropivacaine at three combinations of volumes and concentrations for ultrasound-guided interscalene brachial plexus block would produce different effects in the aspect of onset time, pain control and the incidence of side effects. METHODS: Ninety-nine patients undergoing elective arthroscopic shoulder surgery were randomized to receive an ultrasound guided combined with nerve stimulator mediated interscalene block with ropivacaine 0.75 % (6.7 ml, Group 0.75), 0.5 % (10 ml, Group 0.5) or 0.25 % (20 ml, Group 0.25). The primary end point was the onset time of the sensory blockade, assessed by using a pinprick in the C5-6 dermatome. The secondary end points included the onset time of the motor blockade, block success rate, postoperative pain rating score, rescue analgesics requirement, sleep quality, strength of the hand on the block side,and the incidence of hemi-diaphragmatic paresis which was evaluated by ultrasonography. RESULTS: There was a statistically significant difference of the sensory block median onset times among Group 0.75 (5 min), Group 0.5 (10 min) and Group 0.25 (20 min). One patient in Group 0.5 and 20 patients in Group 0.25 did not achieve a complete motor block within 30 min, which were also significantly different. No significant difference was observed in postoperative analgesia, decrease of handgrip strength and the incidence of hemi-diaphragmatic paresis among the 3 groups. CONCLUSIONS: This study demonstrates that ropivacaine 50 mg as 0.25, 0.5 or 0.75 % solution for interscalene brachial plexus block before arthroscopic shoulder surgery produces comparable blockade with few side effects, while 0.75 % seems to be more preferable as it is associated with faster onset time. TRIAL REGISTRATION: ChiCTR-TRC-13004058 . Registered 4 December 2013.

Extrafascial injection for interscalene brachial plexus block reduces respiratory complications compared with a conventional intrafascial injection: a randomized, controlled, double-blind trial.

BACKGROUND: Hemidiaphragmatic paresis after ultrasound-guided interscalene brachial plexus block is reported to occur in up to 100% of patients. We tested the hypothesis that an injection lateral to the brachial plexus sheath reduces the incidence of hemidiaphragmatic paresis compared with a conventional intrafascial injection, while providing similar analgesia. METHODS: Forty ASA I-III patients undergoing elective shoulder and clavicle surgery under general anaesthesia were randomized to receive an ultrasound-guided interscalene brachial plexus block for analgesia, using 20 ml bupivacaine 0.5% with epinephrine 1:200 000 injected either between C5 and C6 within the interscalene groove (conventional intrafascial injection), or 4 mm lateral to the brachial plexus sheath (extrafascial injection). The primary outcome was incidence of hemidiaphragmatic paresis (diaphragmatic excursion reduction >75%), measured by M-mode ultrasonography, before and 30 min after the procedure. Secondary outcomes were forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow. Additional outcomes included time to first opioid request and pain scores at 24 h postoperatively (numeric rating scale, 0-10). RESULTS: The incidences of hemidiaphragmatic paresis were 90% (95% CI: 68-99%) and 21% (95% CI: 6-46%) in the conventional and extrafascial injection groups, respectively (P<0.0001). Other respiratory outcomes were significantly better preserved in the extrafascial injection group. The mean time to first opioid request was similar between groups (conventional: 802 min [95% CI: 620-984 min]; extrafascial: 973 min [95% CI: 791-1155 min]; P=0.19) as were pain scores at 24 h postoperatively (conventional: 1.6 [95% CI: 0.9-2.2]; extrafascial: 1.6 [95% CI: 0.8-2.4]; P=0.97). CONCLUSIONS: Ultrasound-guided interscalene brachial plexus block with an extrafascial injection reduces the incidence of hemidiaphragmatic paresis and impact on respiratory function while providing similar analgesia, when compared with a conventional injection. CLINICAL TRIAL REGISTRATION: NCT02074397.

Botulinum Neurotoxins: Qualitative and Quantitative Analysis Using the Mouse Phrenic Nerve Hemidiaphragm Assay (MPN).

The historical method for the detection of botulinum neurotoxin (BoNT) is represented by the mouse bioassay (MBA) measuring the animal survival rate. Since the endpoint of the MBA is the death of the mice due to paralysis of the respiratory muscle, an ex vivo animal replacement method, called mouse phrenic nerve (MPN) assay, employs the isolated N. phrenicus-hemidiaphragm tissue. Here, BoNT causes a dose-dependent characteristic decrease of the contraction amplitude of the indirectly stimulated muscle. Within the EQuATox BoNT proficiency 13 test samples were analysed using the MPN assay by serial dilution to a bath concentration resulting in a paralysis time within the range of calibration curves generated with BoNT/A, B and E standards, respectively. For serotype identification the diluted samples were pre-incubated with polyclonal anti-BoNT/A, B or E antitoxin or a combination of each. All 13 samples were qualitatively correctly identified thereby delivering superior results compared to single in vitro methods like LFA, ELISA and LC-MS/MS. Having characterized the BoNT serotype, the final bath concentrations were calculated using the calibration curves and then multiplied by the respective dilution factor to obtain the sample concentration. Depending on the source of the BoNT standards used, the quantitation of ten BoNT/A containing samples delivered a mean z-score of 7 and of three BoNT/B or BoNT/E containing samples z-scores <2, respectively.

[Levobupivacaine for Ultrasound-guided Interscalene Block: Block with 6 ml Leads to Less Occurrence of Respiratory Depression and Hemidiaphragmatic Paralysis].

BACKGROUND: Interscalene brachial plexus block (ISBPB) complications depend usually on the dose administered. METHODS: The object of this study was to determine whether ultrasound-guided ISBPB with 6 ml of 0.5% levobupivacaine would reduce occurrence of respiratory depression and hemidiaphragmatic paralysis. RESULTS: Patients undergoing arthroscopic shoulder surgery under nerve block with general anesthesia (n = 20) were recruited. There were no differences between pre and post operative respiratory function (forced expiratory volume 1.0 (sec) % and vital capacity). Hemidiaphragmatic paralysis on postoperative ultrasonography was found in two patients. CONCLUSIONS: The use of low-volume ultrasound-guided ISBPB is associated with less respiratory depression and hemidiaphragmatic paralysis.