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Background: With an aging population, orthopedics has become one of the largest and fastest growing surgical fields. However, data on the use of critical care services (CCS) in patients undergoing orthopedic procedures remain sparse. Purpose: We sought to elucidate the prevalence and characteristics of patients requiring CCS and intermediate levels of care after orthopedic surgeries at a high-volume orthopedic medical center. Methods: We retrospectively reviewed inpatient electronic medical record data (2016–2020) at a high-volume orthopedic hospital. Patients who required CCS and intermediate levels of care, including step-down unit (SDU) and telemetry services, were identified. We described characteristics related to patients, procedures, and outcomes, including type of advanced services required and surgery type. Results: Of the 50,387 patients who underwent orthopedic inpatient surgery, 1.6% required CCS and 21.6% were admitted to an SDU. Additionally, 482 (1.0%) patients required postoperative mechanical ventilation and 3602 (7.1%) patients required continuous positive airway pressure therapy. Spine surgery patients were the most likely to require any form of advanced care (45.7%). Conclusions: This retrospective review found that approximately one-fourth of orthopedic surgery patients were admitted to units that provided critical and intermediate levels of care. These results may prove useful to hospitals in estimating needs and allocating resources for advanced and critical care services after orthopedic surgery.

BackgroundArthroplasty is one of the most commonly performed procedures in the USA with projections of continuous growth. As this field undergoes continuous changes, the goal of this study was to provide an analysis of patient-related and healthcare system-related trends. This is important as it allows practitioners, administrators and policy makers to allocate needed resources appropriately.MethodsThe study included total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures from 2006 to 2016. Demographic information, comorbidities and complications were extracted and analyzed from the Premier Healthcare database.ResultsThe surgical volume increased annually over the observation period by an average of 5.54% for TKA and 7.02% for THA, respectively. The average age of the patient population and the types of anesthesia used remained relatively consistent over time. Comorbidity burden increased, especially for obesity (16.52% in 2006 and 29.77% in 2016 for TKA, 11.15% in 2006 and 20.92% in 2016 for THA), obstructive sleep apnea (OSA) (6.82% in 2006 and 17.03% in 2016 for TKA, 4.69% in 2006 and 12.72% in 2016 for THA) and renal insufficiency (2.81% in 2006 and 7.01% in 2016 for TKA, 2.78% in 2006 and 6.43% in 2016 for THA). Minor trends of increases were also observed in the prevalence of liver disease, depression and hypothyroidism. All postoperative complications were trending lower except for acute renal failure, where an increase was noted (4.39% in 2006 and 8.10% in 2016 for TKA, 4.99% in 2006 and 8.42% in 2016 for THA).DiscussionSignificant trends in the care of patients who undergo TKA and THA were identified. Individuals undergoing these procedures presented with a higher prevalence of comorbidities. Despite these trajectories, complications declined over time. These data can be used to inform future research and to allocate resources to address changes in populations cared for and complications encountered.

Femoral and axillary cannulation for arterial inflow in acute type A aortic dissection are the most commonly used cannulation strategies in current practice. More recently, our group and others have successfully used a central cannulation technique with excellent results. Although this approach has been described, specific technical details have not been clearly defined. In addition, the ideal anatomic characteristics of different types of aortic dissections amenable to central cannulation have not been delineated. The purpose of this brief communication is to describe the technical and procedural details specific to cannulation of the dissected ascending aorta and to propose a classification scheme of ascending aortic dissection anatomy based on difficulty of central cannulation.

Compare treatment persistence, healthcare utilisation and costs for patients treated with escitalopram versus other SSRI/SNRIs in a real-world setting.Patients with a diagnosis for major depressive disorder (MDD) and at least one prescription for an SSRI or SNRI were identified from the Ingenix Impact Database (2002-2005). The baseline and study observation periods were defined as the 6 months before and after the index date (first date for an SSRI /SNRI pharmacy claim). Comparisons were made between patients initiated on escitalopram versus other SSRI/SNRIs using descriptive statistics and multivariate regressions.Escitalopram patients (n=10,465) had better treatment persistence compared to patients initiated on other SSRI/SNRIs (n=28,310): the hazard ratio of all discontinuation was 0.96 (95% confidence interval [CI]=0.94-0.99) for the escitalopram therapy (p=0.003), and the hazard ratio of switching to another second-generation antidepressant was 0.91 (95% CI=0.87-0.94) for the escitalopram therapy (p0.001). Escitalopram patients also had fewer inpatient service and emergency room visits. Adjusted average total all-cause healthcare costs and inpatient services costs were $839 and $405 lower in the escitalopram group (both p0.05).Escitalopram may be associated with lower healthcare utilisation and costs among adult MDD patients compared to other SSRI/SNRIs.

To assess treatment persistence, hospitalization outcomes and mean healthcare costs of geriatric major depressive disorder (MDD) patients treated with escitalopram compared to other selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).Patients agedor = 65 years with at least one inpatient claim or two independent claims associated with MDD diagnosis were identified in the IHCIS National Managed Care Database (2003-2005). Patients were continuously enrolled for at leastor = 12 months, filled at least one prescription for an SSRI/SNRI and did not use any second-generation antidepressant during the 6 months pre-index date. Unadjusted and multivariate analyses adjusting for baseline characteristics were conducted.Treatment persistence, hospitalization utilization, and average prescription drug, medical, and total healthcare costs were compared between patients initiated on escitalopram versus other SSRI/SNRIs.Escitalopram-treated patients (N = 459) were less likely to discontinue treatment (HR = 0.85, p = 0.012) or switch to another second-generation antidepressant (HR = 0.76, p = 0.006) compared to patients treated with other SSRI/SNRIs (N = 1517). Escitalopram-treated patients had 39% fewer hospitalization days (p = 0.004). Both groups had similar mean prescription drug costs ($1659 vs. $1630, p = 0.687). After controlling for baseline characteristics, escitalopram-treated patients had lower mean total medical service costs ($9425 vs. $12,703, p0.001) and mean total healthcare costs ($11,043 vs. $14,163, p0.001).This study's limitations include its small sample size, short observational periods and exclusivity of indirect costs.Geriatric patients treated with escitalopram had higher treatment persistence, fewer hospitalization days and lower total healthcare costs than patients on other SSRI/SNRIs after controlling for baseline characteristics. Most of the cost savings were due to reductions in hospitalizations.

To compare escitalopram versus citalopram for the treatment of major depressive disorder (MDD) in geriatric patients.Administrative claims data (2003-2005) were analyzed for patients agedor =65 years with at least one inpatient claim or two independent medical claims associated with MDD diagnosis. Patients were continuously enrolled for at least 12 months, filled at least one prescription for citalopram or escitalopram and had no second generation antidepressant use during the 6-month pre-index date. Contingency table analysis and survival analysis were used to compare outcomes between the two treatment groups.Treatment persistence, hospitalization utilization, and prescription drug, medical, and total healthcare costs were analyzed. Outcomes were compared between patients initiated on escitalopram and those initiated on citalopram both descriptively and using multivariate analysis adjusting for baseline characteristics.Among 691 geriatric patients, escitalopram-treated patients (n=459) were less likely to discontinue treatment (hazard ratio [HR]=0.83, p=0.049) or switch to another second generation antidepressant (HR=0.62, p=0.001) compared to patients treated with citalopram (n=232). Patients treated with escitalopram had a significantly lower hospitalization rate (31.2% vs. 38.8%, p=0.045) and 66% fewer hospitalization days based on negative binomial regression (p0.001). While escitalopram patients had comparable prescription drug costs, they had lower total medical service costs (regression: $9748 vs. $19,208, p0.001) and lower total healthcare costs (regression: $11,434 vs. $20,601, p0.001).This study's limitations include its small sample size, short observational periods and exclusivity of indirect costs.Geriatric patients treated with escitalopram had better treatment persistence, fewer hospitalizations, and lower medical and total healthcare costs than patients treated with citalopram. Most of the cost reduction was attributable to significantly lower hospitalizations and total medical costs.

To describe dosing patterns for tumor necrosis factor (TNF) antagonists in patients with rheumatoid arthritis from health care provider and payer point of interest.Using privately insured US claims data from 31 large employers covering 31 companies across the US, rheumatoid arthritis (RA) patients were identified and three cohorts were defined based on first TNF-antagonist treatment (adalimumab, etanercept, or infliximab) administered after January 1, 2003. Dosage-adjustment patterns were assessed during the following 12-month period. Changes in dosage (both increases and decreases) and maintenance of a stable dosage were evaluated. For the health care provider point of interest, a new algorithm was developed to assess treatment patterns with chronic injectable therapies that incorporated the potential inconsistency between days of supply and prescription-gap data, thus providing the actual use of TNF-antagonist treatment. For the payer, usage data addressed whether the TNF antagonist was used at a greater dosage than recommended. Differences in baseline characteristics and dosage change rates between cohorts were tested using Chi-Square tests for categorical variables and Wilcoxon tests for continuous variables.From the health care provider point of interest, 83.4% of adalimumab-treated patients (n = 205) initially received the recommended dosage, 10.2% received less, and 6.3% received more; 87.7% of etanercept-treated patients (n = 455) initially received the recommended dosage, 11.2% received less, and 1.1% received more; and 83.8% of infliximab-treated patients (n = 148) started with 2-4 vials (the recommended dosage is based on the weight of the patient, not total milligrams). All treatments had similar dosage decrease and discontinuation rates. Maintenance of stable dosage was lower for infliximab (20.9%) than adalimumab (37.1%) and etanercept (39.1%); both p0.01. The infliximab dosage-increase rate (35.1%) was greater than adalimumab (3.9%) and etanercept (0); both p0.01. From the payer point of interest, dosage-increase rate was greater for infliximab (28.3%) than adalimumab (8.7%) and etanercept (6.9%), both p0.01.Infliximab had greater dosage-increase rates than adalimumab and etanercept. Adalimumab and etanercept had similar dosage-increase rates. All treatments had similar dosage-decrease and discontinuation rates. Maintenance of stable dosage was lower for infliximab than for adalimumab and etanercept. The study has the usual limitation of claims data analysis in that clinical details might be insufficient to draw causal inference.

To compare the cost of care for rheumatoid arthritis (RA) patients treated with adalimumab, infliximab, and etanercept.RA patients were identified from a privately insured database. Three mutually exclusive treatment cohorts were formed based on the date of first tumor necrosis factor (TNF) antagonist treatment (index date) after January 1, 2003. Baseline characteristics were assessed in the 3-month pretreatment period. Healthcare (i.e., medical service and prescription medications) utilization and cost were assessed for the following 12 months. RA-related medical cost included the total cost for medical service associated with RA diagnosis. RA-related healthcare cost included RA-related medical and drug cost. Uneven distribution of baseline characteristics were adjusted with the propensity score method. Cost was compared between treatment cohorts.Twelve-month TNF-antagonist therapy cost ($12 853 vs. 17 299, p = 0.002), total RA-related drug cost ($13 794 vs. 17 647, p = 0.006), total RA-related medical cost ($971 vs. 2920, p0.001), total RA-related healthcare cost ($14 764 vs. 20 566, p = 0.002), and total drug cost ($16 210 vs. 19 769, p = 0.028) were significantly less for adalimumab (n = 217) than infliximab (n = 234). Twelve-month healthcare cost for adalimumab was comparable to etanercept (n = 546).Annual healthcare cost for adalimumab patients was significantly less than for infliximab patients and was comparable to etanercept patients. This analysis is subject to the usual limitation of claims data analyses in that few clinical details are available and causal inference conclusions are limited.

Background— Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell–derived factor 1-α (engineered stromal cell–derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction. Methods and Results— Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical–initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls. Conclusions— We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.

Objective The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell–derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction. Methods Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. Results Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle. Conclusions Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.

Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry–based metabolite profiling platform to 36 patients undergoing alco-hol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myo-cardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream con-tributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiogra-phy with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and sug-gest that similar approaches may be used for detection or prediction of other disease states.

Many therapies exist for treating adult attention-deficit/hyperactivity disorder (ADHD), also referred to as attention-deficit disorder (ADD), but there is no research regarding cost differences associated with initiating alternative ADD/ADHD drug therapies in adults.To compare from the perspective of a large self-insured employer the risk-adjusted direct health care costs associated with 3 alternative drug therapies for ADD in newly treated patients: extended-release methylphenidate (osmotic release oral system-MPH), mixed amphetamine salts extended release (MAS-XR), or atomoxetine.We analyzed data from a US claims database of 5 million beneficiaries from 31 large self-insured employers (1999-2004). Analysis was restricted to adults aged 18 to 64 years with at least 1 diagnosis of ADD/ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 314.0x--attention deficit disorder; 314.00--attention deficit disorder without hyperactivity; or 314.01--attention-deficit disorder with hyperactivity) and at least 1 pharmacy claim for OROS-MPH, MAS-XR, or atomoxetine identified using National Drug Codes. In preliminary analysis, we calculated the duration of index ADHD drug therapy as time from index therapy initiation to a minimum 60-day gap. Because the median duration of index ADHD drug therapy was found to be approximately 90 days, the primary measures were total direct medical plus drug costs and medical-only costs computed over 6 months following therapy initiation. Adults were required to have continuous eligibility 6 months before and 6 months after their latest drug therapy initiation and no ADHD therapy during the previous 6 months. Cost was measured as the payment amount made by the health plan to the provider rather than billed charges, and it excluded patient copayments and deductibles. Medical costs included costs incurred for all-cause inpatient and outpatient/other services. Costs were adjusted for inflation to 2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index.Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P0.001); the risk-adjusted total direct costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD.After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on average, slightly lower medical and total medical and drug costs than those treated with MAS-XR or atomoxetine over the 6-month period after drug therapy initiation. Approximately 30% of the cost difference compared with MAS-XR was attributable to 1 high-cost outlier with medical diagnoses for the highest-cost claim that were unrelated to ADHD.

Obesity is highly prevalent among patients with type 2 diabetes. Unfortunately, weight gain may also be a consequence of some antidiabetic medications. Although clinical benefits of weight loss have been established, the economic consequence of weight change among patients with type 2 diabetes is unclear.The objective was to measure 1-year total and diabetes-related health care costs associated with weight change during the preceding 6-month period among type 2 diabetic patients on antidiabetic therapy.Administrative claims, electronic laboratory data and medical chart information were abstracted for continuously enrolled adults with type 2 diabetes from an health maintenance organization (HMO) for the period from July 1, 1997 through October 31, 2005. To assess the economic impact of weight change, three regression models were applied to estimate the following: (1) the effect of weight change in general (one-slope model); (2) the different effects of weight gain and no weight gain (two-slope model); and (3) the different effects of weight gain and no weight gain (i.e., no change or weight loss) among obese and non-obese patients (four-slope model). Patients included in the study had a baseline weight measurement and a second weight measurement approximately 6 months later. They were also required to be on at least one antidiabetic drug therapy within 1 month around the baseline weight measurement date (index date). Based on the measured weight change, patients were classified into two groups--weight gainers and non-weight gainer. Total health care cost and diabetes-related cost were measured during the 1-year period following the second weight measurement and were adjusted to 2004 dollars by the medical component of the Consumer Price Index (CPI). Generalized linear models with log link function and gamma distribution were applied to assess the impacts of weight change on the 1-year total health care cost as well as 1-year diabetes-related cost. All models controlled for patients' baseline demographics, comorbidities, body mass index (BMI), glycosylated hemoglobin (HbA1c), and prior resource utilization.The study included 458 patients, of whom 224 (48.9%) experienced minimum weight gain of 1 pound between the two weight measurements. The average 1-year total health care cost following the second weight measure was $6382 and the diabetes-related cost was $2002. The mean total health care cost was $7260 for the weight-gainers and $5541 for the non-weight gainers (p = 0.046), and the mean diabetes-related cost, respectively, was $2141 and $1869 (p = 0.006). Results from the models showed that one percentage point of weight change was positively associated with a 3.1% ($213, p0.01) change in total health care cost. When weight gain and no gain were modeled separately, one percentage point of weight loss was associated with a 3.6% ($256, p0.05) decrease in total health care cost and a 5.8% ($131, p0.01) decrease in diabetes-related cost. However, one percentage point of weight gain was not associated with significant increase in either total health care or diabetes-related cost. Further, results from the model with interactions between weight change and obesity status revealed that the economic benefit of weight loss was more pronounced in the obese group (BMIor = 30). Log likelihood ratio tests showed that the one-slope model for total health care cost and the two-slope model for diabetes-related cost are the appropriate models of choice.Weight loss significantly reduced diabetes-related costs. Controlling for baseline factors in the regression model, the 1-year total health care cost following 1% weight loss (or gain) was $213 cost decrease (or increase). Diabetes-related cost did not appear to be associated with weight gain. Economic benefit of weight loss was evident among type 2 diabetic patients on antidiabetic therapy, especially among obese patients.

Focal muscle contracture in the limb following sytemic administration of depolarizing neuromuscular blocking agents have been demonstrated experimentally with transection or crush injury of the nerve, but has rarely been observed clinically in patients with partial peripheral nerve injury. Three cases of spastic response in the hand and wrist are described in patients with subclinical chronic, subacute, and acute nerve injury, to document the occurrence of this phenomenon under various circumstances.

Serum concentration of d-tubocurarine decreases rapidly after intravenous injection because of uptake and distribution. The circulating residue of an ED 50 dose of d-tubocurarine five minutes after injection will produce no block in a previously unexposed neuromuscular junction. To produce a 50 per cent block with the circulating d-tubocurarine residue in a previously unexposed neuromuscular junction requires an initial injection of 2.5 x ED 50 dose. Five minutes after a dose 5 to 6 times the ED 50, the plasma d-tubocurarine residue is sufficient to produce a total block.

Forty patients (A.S.A. class I or II), 18 to 75 years of age, who were undergoing elective surgery were studied to determine the clinical and subclinical neuromuscular blocking effects of two antibiotics, tobramycin and gentamicin and to compare these effects with those produced by cefazolin, an aminoglycoside not known to produce paralysis. Patients were prospectively and randomly assigned in approximately equal numbers to one of four groups: group A received 1 mg/kg of tobramycin; group B, 1 mg/kg of gentamicin; group C, 500 mg of cefazolin; or group D, control (no antibiotic). Antibiotics were administered intravenously 45 minutes immediately preceding the study. The ulnar nerve was stimulated supramaximally and neuromuscular function was measured electromyographically. Anesthesia was induced with thiopental, 4 mg/kg IV, and maintained with endotracheal enflurane 1.0% to 1.5% (inspired) and N2O-O2 (2 L:1 L) after intubation. Succinylcholine (1 mg/kg) was administered after induction of anesthesia and the magnitude and duration of neuromuscular block monitored. d-Tubocurarine (0.1 mg/kg) was given 5 to 10 minutes after full recovery from succinylcholine and repeated as required. At the end of the operation, atropine, 0.02 mg/kg, and neostigmine, 0.4 mg/kg, were used to reverse the block. Base line neuromuscular data, duration of block of succinylcholine, and potency, duration of block, recovery rate, train-of-four fade, tetanic trend, response to double stimuli, post-tetanic effect, and reversibility of the subsequent d--tubocurarine-induced neuromuscular block were not significantly different (p less than 0.01) between any two groups. Tobramycin, gentamicin, and cefazolin, in recommended single doses, lack clinical neuromuscular blocking and subclinical relaxant-potentiating effects.

Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch ("facilitation") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane.

The neuromuscular sensitivity of 71 patients (A.S.A. class I or II) was tested by scoring on a scale from 1 to 6 the ability to lift the upper eyelid 2 minutes after pretreatment with 1 mg of pancuronium. Subsequently, each patient also received an additional "intubation dose" pancuronium (in milligrams) equal to the eye-opening test score (group I), or either 1 mg (group II) or 2 mg (group III) in excess. The resultant depression of the neurally evoked muscle response of the little finger was quantified by another score (the response score) which allowed for assessment of neuromuscular block beyond the limit of 100% depression of the twitch. The criteria for the response score, in the response score, in the order of increasing magnitude of block, were: (1) visible twitch responses to all 4 of the train-of-four stimulation remained; (2) part of the train-of-four twitches was eliminated; (3) all twitches were eliminated; (4) tetanus was eliminated; (5) post-tetanic twitch following a 5-second 50 Hz tetanus was also eliminated; and (6) not even the post-tetanic twitch became elicitable again in 30 minutes. It was found that 1 mg of pancuronium depressed the eye-opening score to 4.0 +/- 0.2, from 5.1 +/- 0.1 (mean +/- SEM, p < 0.01). Following the additional "intubation dose" of pancuronium, patients in group I had an average response score of 2.2 +/- 0.3, those in group II a score of 3.4 +/- 0.2, and those in group III, a score of 4.8 +/- 0.6. Each additional 1 mg of pancuronium (increasing from group I to III) linearly increased the average response score. In terms of frequency response, patients in group I had more than a 50% change of being scored 1, while those in group II had a greater than 50% chance of being scored 3, 4, or 5, and those in group III had more than a 50% chance of being scored 6. It is concluded that sensitivity to pancuronium can be quantified by the ptotic response to a 1-mg test dose of pancuronium, and that a sensitivity-adjusted additional "intubation dose" of pancuronium can be predetermined in individual patients.