Harald Groeben

Accelerometry of Adductor Pollicis Muscle Predicts Recovery of Respiratory Function from Neuromuscular Blockade

Background Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers. Methods Rocuronium (0.01 mg/kg + 2–10 &mgr;g · kg−1 · min−1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with “acceptable” pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of ≥90% of baseline) was calculated using a linear regression model. Results At peak blockade (TOF ratio 0.5 ± 0.16), forced inspiratory flow was impaired (53 ± 19%) to a greater degree than forced expiratory flow (75 ± 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 ± 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22–0.71) predicts “acceptable” recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82–1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively. Conclusion Impaired inspiratory flow and upper airway obstruction frequently occur during minimal neuromuscular blockade (TOF ratio 0.8), and extubation may put the patient at risk. Although a TOF ratio of unity predicts a high probability of adequate recovery from neuromuscular blockade, respiratory function can still be impaired.

Postoperative upper airway obstruction after recovery of the train of four ratio of the adductor pollicis muscle from neuromuscular blockade.

Anesthetics, and even minimal residual neuromuscular blockade, may lead to upper airway obstruction (UAO). In this study we assessed by spirometry in patients with a train-of-four (TOF) ratio >0.9 the incidence of UAO (i.e., the ratio of maximal expiratory flow and maximal inspiratory flow at 50% of vital capacity [MEF50/MIF50] >1) and determined if UAO is induced by neuromuscular blockade (defined by a forced vital capacity [FVC] fade, i.e., a decrease in values of FVC from the first to the second consecutive spirometric maneuver of ≥10%). Patients received propofol and opioids for anesthesia. Spirometry was performed by a series of 3 repetitive spirometric maneuvers: the first before induction (under midazolam premedication), the second after tracheal extubation (TOF ratio: 0.9 or more), and the third 30 min later. Immediately after tracheal extubation and 30 min later, 48 and 6 of 130 patients, respectively, were not able to perform spirometry appropriately because of sedation. The incidence of UAO increased significantly (P < 0.01) from 82 of 130 patients (63%) at preinduction baseline to 70 of 82 patients (85%) after extubation, and subsequently decreased within 30 min to values observed at baseline (80 of 124 patients, 65%). The mean maximal expiratory flow and maximal inspiratory flow at 50% of vital capacity ratio after tracheal extubation was significantly increased from baseline (by 20%; 1.39 ± 1.01 versus 1.73 ± 1.02; P < 0.01), and subsequently decreased significantly to values observed at baseline (1.49 ± 0.93). A statistically significant FVC fade was not present, and a FVC fade of ≥10% was observed in only 2 patients after extubation. Thus, recovery of the TOF ratio to 0.9 predicts with high probability an absence of neuromuscular blocking drug-induced UAO, but outliers, i.e., persistent effects of neuromuscular blockade on upper airway integrity despite recovery of the TOF ratio, may still occur.

High Thoracic Epidural Anesthesia Does Not Alter Airway Resistance and Attenuates the Response to an Inhalational Provocation Test in Patients with Bronchial Hyperreactivity

BackgroundThe functional relevance of an intact pulmonary sympathetic innervatlon for airway resistance is unknown. We therefore evaluated whether or not pulmonary sympathetic denervation by thoracic epidural anesthesia decreases the threshold of an inhalational provocation with acetylcholine in 20 patients with documented bronchial hyperreactivity scheduled for elective upper abdominal or thoracic surgery. MethodsBaseline inhalational provocation with acetylcholine was performed 2–4 days before surgery. The acetylcholine threshold concentration for a hyperreactivity response (i.e., for a 20% decrease in forced expiratory volume in 1 s and a 100% increase in total respiratory resistance by oscillometry) was determined. On the day of surgery a second inhalatlve provocation with acetylcholine was performed 45 min after the patients had received 6–8 ml epidural bupivacaine 0.75% (n = 10), intravenous bupivacalne (1.2 mg * min-1, n = 6), or 6–8 ml epidural saline (n = 4). The acetylcholine threshold concentration for a hyperreactive response was again determined. We also measured vital capacity, forced expiratory volume in 1 s as a percentage of vital capacity, spread of sensory blockade (pin prick), skin temperature on hand and foot (telethermography). ResultsDuring thoracic epidural anesthesia, C4-T8 skin temperature increased significantly on hand and foot indicating widespread sympathetic blockade including the lungs. Compared to values obtained immediately before pulmonary sympathetic blockade, forced expiratory volume in 1 s as a percentage of vital capacity, and total respiratory resistance by oscillometry remained unchanged, while vital capacity decreased. Compared to baseline the acetylcholine threshold concentration for the hyperreactive response increased threefold after epidural as well as after intravenous bupivacaine. Epidural saline evoked no directional changes in the acetylcholine threshold concentration. ConclusionsWe conclude that in patients with bronchial hyperreactivity 1. blockade of pulmonary sympathetic innervation seems to be of no relevance for airway resistance and 2. both epidural and intravenous bupivacaine substantially attenuate the response to an inhalational provocation with acetylcholine.

Effects of the α2-Adrenoceptor Agonist Dexmedetomidine on Bronchoconstriction in Dogs

BackgroundTracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that &agr;2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective &agr;2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown. MethodsAfter the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 &mgr;g/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated. ResultsAt baseline, histamine constricted the airways to 66 ± 27% (mean ± SD) (P < 0.0001) and 59 ± 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 ± 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 ± 30% of maximum; P < 0.0001 compared with histamine alone). Conclusion&agr;2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.

Intravenous lidocaine and bupivacaine dose-dependently attenuate bronchial hyperreactivity in awake volunteers

Background In standard textbooks, intravenous lidocaine is recommended for intubation of patients with bronchial hyperreactivity. However, whether and to what extent intravenous local anesthetics attenuate bronchial hyperreactivity in humans is unknown. Accordingly, nine awake volunteers with known bronchial hyperreactivity were subjected to an inhalational challenge with acetylcholine before and during intravenous infusion of lidocaine, bupivacaine, or placebo in a randomized, double‐blinded fashion. Methods Baseline acetylcholine threshold concentrations were determined 3–5 days before initiation of the investigation. The response to the acetylcholine challenge was defined as hyperreactive, if forced expiratory volume in 1 s decreased by at least 20%. In addition, the acetylcholine threshold for a 100% increase in airway resistance was obtained by body plethysmography. On seven different days, the acetylcholine challenge was repeated at the end of a 30‐min intravenous infusion period of three doses of lidocaine (1, 3, and 6 mg *symbol* min sup ‐1) or bupivacaine (0.25, 0.75, and 1.5 mg *symbol* min sup ‐1), during saline placebo infusion, respectively. Acetylcholine‐threshold concentrations were presented with the respective plasma concentrations of the local anesthetic. Results The infusion of lidocaine and bupivacaine resulted in plasma concentrations (means+/‐SD) of 0.29+/‐0.11, 1.14 +/‐0.39, and 2.02+/‐0.5 micro gram *symbol* ml sup ‐1 for lidocaine and 0.11+/‐0.04, 0.31+/‐0.09, and 0.80 +/‐0.18 micro gram *symbol* ml sup ‐1 for bupivacaine, respectively. Compared to baseline, the acetylcholine threshold for a 20% decrease of forced expiratory volume in 1 s as well as the threshold for a 100% increase in total airway resistance increased significantly with increasing plasma concentrations of both local anesthetics. Compared to placebo, acetylcholine threshold was almost quadrupled for lidocaine and tripled for bupivacaine with the highest plasma concentration of each local anesthetic. Conclusions In awake humans, intravenous lidocaine and bupivacaine both dose‐dependently attenuated the hyperreactive response to a nonspecific inhalational challenge with acetylcholine.

Predictive value of mechanomyography and accelerometry for pulmonary function in partially paralyzed volunteers

Background:  Accelerometry (ACM) of adductor pollicis muscle has been used for monitoring of neuromuscular blockade but its validity compared with the gold standard, mechanomyography (MMG), has been questioned. During neuromuscular blockade we compared these methods and we assessed pulmonary function.

Development and validation of a novel tool to estimate peri-operative blood loss.

Surgical blood loss predicts peri‐operative outcomes. We have developed and validated Blood Loss Scores to estimate peri‐operative blood loss during major abdominal surgery. Surgical blood loss and changes in haemoglobin concentration were recorded intra‐ and postoperatively for 48 h in 100 patients undergoing radical prostatectomy. Data from the first group (n = 50) were used to derive the Blood Loss Scores which were validated against the data from a second group (n = 50) at three time points (immediately postoperative and 24‐ and 48‐h later). The score, taking into account suction fluid volume and haemoglobin concentration, explained more of the variance in the measured blood loss than the experts’ assessment (77% vs 54%, p = 0.05) or the change in haemoglobin concentration (77% vs 11%, p < 0.0001). Addition of the change in haemoglobin concentration improved the estimate for the 24‐ and 48‐h postoperative Blood Loss Scores to explain 78% and 80% of the variance of measured blood loss.

Pulmonary sympathetic denervation does not increase airway resistance in patients with chronic obstructive pulmonary disease (COPD)

Whether or not neural blockade of pulmonary sympathetic innervation is of relevance for airway resistance in patients with chronic obstructive pulmonary disease (COPD) is unknown. Accordingly we evaluated airway resistance during sympathetic blockade by high thoracic epidural anaesthesia in patients with COPD. Before and 45 min after thoracic epidural injection of bupivacaine 0.75% (6–8 ml; n=10) total respiratory resistance (oscillometry, Ros), vital capacity (VC), forced expiratory vital capacity in 1 s (FEV1, [% VC]), functional residual capacity (FRC; helium dilution method), and arterial blood gases were measured. Three additional patients received bupivacaine intravenously (1.2 mg . min‐1 for 45 min), another three received saline epidurally. Sensory blockade covered segment C5 through T8. As an indicator of widespread sympathetic blockade including the lungs, skin temperature increased significantly on thumb and little toe. Despite pulmonary sympathetic denervation Ros, FEV1, and FRC remained unchanged, while VC decreased slightly, probably due to intercostal muscle blockade. Blood gases remained constant. Neither intravenous bupivacaine nor epidural saline evoked directional changes. Since, in contrast to β‐adre‐noceptor blockade, pulmonary sympathetic denervation did not increase airway resistance in patients with COPD, neural sympathetic blockade seems to be of no relevance for airway resistance in these patients.

Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery

OBJECTIVE Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy. METHODS All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis. RESULTS 739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival. CONCLUSIONS Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series

Background. Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the influence of an &agr;-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without &agr;-receptor blockade undergoing surgery for catecholamine producing tumours. Methods. Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) &agr;-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI). Results. No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024). Conclusions. Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an &agr;-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative &agr;- receptor blockade for phaeochromocytoma surgery demands further study.