The Utility of Grip Strength as a Simplified Measure of Frailty in the Older Adult in the Preoperative Clinic.

Objective  The aim of this study was to compare the measure of grip strength against other validated methods of measuring frailty. Materials and methods This was a single-center, cross-sectional study that took place at the Westchester Medical Center Pre-Procedural Testing Clinic. The patient population included n = 73 patients ≥65 years of age evaluated for elective surgery. During the study, patients' grip strength, CFS-I (Clinical Frailty Score of Investigator), CFS-P (Clinical Frailty Score of Participant), and FRAIL (Fatigue, Resistance, Aerobic capacity, Illnesses, and Loss of weight) scores were measured. Results Grip strength correlated negatively with the CFS-I, CFS-P, and FRAIL scores for females. Reduced grip strength in females correlated with higher frailty scores and vice versa. Male grip strength showed no significant relationship with the frailty scales. In addition, multivariate linear regression analysis revealed that the independent measure that demonstrated a significant inverse association with grip strength was age (ß= -0.43, p = <0.001). Conclusions  There exists a difference in the utility of grip strength as a measure of frailty between males and females.

Gender Differences in the Language of LORs Written for Anesthesiology Medical Student Applicants: Analysis of One Program's Recruitment Cycle.

BACKGROUND: Prior studies have demonstrated gender differences in language used in letters of recommendation (LOR) for residency applicants. No previous studies have investigated linguistic gender differences in LOR specifically in the field of anesthesiology. The objective of this study is to determine whether there are potential gender biases in the language of LOR written for anesthesiology residency applicants. METHODS: Letters sent through the Electronic Residency Application Service in application for a single training program in the Northeast in 2019-2020 were divided into self-identified male and female groups. The letters were deidentified, converted to machine-readable text, and input into software to analyze differences in language use. Differences in language use and word count between the 2 groups were compared. RESULTS: Included in this analysis were 316 applicants (113 female applicants and 203 male applicants) who submitted a total of 1132 letters, 409 of which were letters written for females and 723 were written for males. Analysis of 4 document characteristics and 19 psychological construct word categories showed that males had a higher frequency of tentative notations (P < .0110), while females had a higher frequency of ability notations (P < .0449). No other meaningful differences were found. CONCLUSIONS: While our results demonstrated 2 differences in language use between male and female anesthesiology residency applicants for LOR, it is reassuring that LOR are relatively free of linguistic bias. Future research should focus on identifying other areas of the specialty's recruitment process in order to recognize and mitigate gender differences in anesthesiology.

Exploring the transversus abdominis plane block in cesarean sections and the subsequent toxicity risk to neonates via breast milk.

The transversus abdominis plane (TAP) block with its wide application has shown to be an analgesic effective for use in abdominal surgeries, including for cesarean section. However, the bupivacaine delivered in the TAP block comes with the risk of toxicity, both central nerve system (CNS) and cardiovascular system, and has been shown in some instances to reach maximum serum concentrations in excess of the 2 µg/mL associated with the lower end of CNS toxicity. There is a specific concern with cesarean section TAP blocks of the anesthetic passage to the neonate via maternal breast milk and whether this poses a toxicity risk. Bupivacaine has been shown to pass into maternal milk at concentrations 0.34 times the maternal serum concentration. Preliminary statistical analyses suggest that the bupivacaine delivered in breast milk is not in concentrations high enough to cause neonatal toxicity, but further studies would be useful in identifying what the toxicity risk is, if any, to the neonates' breastfeeding after the delivery and TAP block.

Clinical oversight and the avoidance of repeat induced abortion.

OBJECTIVE: To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. METHODS: A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. RESULTS: A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r2 =0.449, P<0.001), a higher contraceptive efficacy score (r=0.280, P=0.025), and a larger number of clinic visits for contraception (r=0.333, P=0.007). CONCLUSION: A continuum of contact with all of the services of a family planning clinic demonstrated a strong efficacy to limit repeat induced abortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available.

Anti-tumor activity of phenoxybenzamine and its inhibition of histone deacetylases.

The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity. Phenoxybenzamine is approved by the United States Food and Drug Administration for the treatment of hypertensive crises associated with tumors of the adrenal medulla, pheochromocytomas. It has several "off label" indications relative to its capacity to relax vascular smooth muscle and smooth muscle of the urogenital tract. The drug also has a long history of apparent efficacy in ameliorating, and perhaps reversing, the severe symptoms of neuropathic pain syndromes. Our interest in this feature of the drug relates to the fact that certain types of neuropathic pain, in particular complex regional pain syndrome, demonstrate a proliferative nature, with the capacity to spread from an injured limb, for example, to a non-injured limb and perhaps to essentially the entire body. Sensory neuronal sprouting in the spinal cord has been observed under conditions where there is a high sensory input from painful stimuli. Searches of gene expression signatures in the BroadBuild02 Molecular Signature Database using their connectivity map software suggested that phenoxybenzamine may have histone deacetylase inhibitory activity. Studies by others have reported inhibitory effects of phenoxybenzamine on growth, invasion and migration of human tumor cell cultures and, in one study, inhibition of tumor expansion in animal experiments. Inhibitory effects on human tumor cell cultures are also reported in the present study. Phenoxybenzamine was also found to have histone deacetylase inhibitory activity; histone deacetylase isoforms 5, 6, and 9 were the most sensitive to inhibition by phenoxybenzamine. The importance of elevated levels of these isoforms as biomarkers of poor prognosis in human malignant disease, and the recognized suppression of tumor growth that may accrue from their inhibition, opens consideration of possible translation of phenoxybenzamine to new clinical applications. This might be facilitated by the fact that phenoxybenzamine is already an approved drug entity. There appears to be no previous report of the activity of phenoxybenzamine as a histone deacetylase inhibitor.

Intraoperative Blood Loss during Induced Abortion: A Comparison of Anesthetics.

OBJECTIVE: To determine whether there is a difference in intraoperative bleeding with inhalational versus noninhalational anesthetic agents for patients undergoing suction dilatation and curettage for first-trimester induced abortion. METHODS: This is an IRB-approved retrospective chart review of the electronic medical records of patients undergoing induced abortion at gestational ages between 5 0/7 and 14 0/7 weeks of pregnancy at the New York City Health + Hospitals/Metropolitan. The records of 138 patients who underwent suction dilatation and curettage for induced abortion between June 2012 and June 2014 were reviewed for an association between anesthetic technique and intraoperative hemorrhage. Twenty patients received inhalational anesthetic agents, while 118 received intravenous anesthetics. Blood loss was estimated by the operating gynecologists. RESULTS: The mean intraoperative blood loss for inhalational anesthetics (113.6 ml) was significantly higher than with noninhalational agents (40.2 ml) (p=0.007). Age, body mass index, and gestational age were not statistically different between the groups; the number of methylergonovine doses at induced abortion trended higher with inhalation anesthetics. CONCLUSIONS: The difference in blood loss between the two types of anesthetic techniques was statistically significant. These findings may be important for patients with significant anemia or at an increased risk of bleeding, such as those with unrecognized coagulopathies.

Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample.

BACKGROUND: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful. METHODS AND FINDINGS: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing. CONCLUSIONS: This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

Phenoxybenzamine in complex regional pain syndrome: potential role and novel mechanisms.

There is a relatively long history of the use of the α -adrenergic antagonist, phenoxybenzamine, for the treatment of complex regional pain syndrome (CRPS). One form of this syndrome, CRPS I, was originally termed reflex sympathetic dystrophy (RSD) because of an apparent dysregulation of the sympathetic nervous system in the region of an extremity that had been subjected to an injury or surgical procedure. The syndrome develops in the absence of any apparent continuation of the inciting trauma. Hallmarks of the condition are allodynia (pain perceived from a nonpainful stimulus) and hyperalgesia (exaggerated pain response to a painful stimulus). In addition to severe, unremitting burning pain, the affected limb is typically warm and edematous in the early weeks after trauma but then progresses to a primarily cold, dry limb in later weeks and months. The later stages are frequently characterized by changes to skin texture and nail deformities, hypertrichosis, muscle atrophy, and bone demineralization. Earlier treatments of CRPS syndromes were primarily focused on blocking sympathetic outflow to an affected extremity. The use of an α -adrenergic antagonist such as phenoxybenzamine followed from this perspective. However, the current consensus on the etiology of CRPS favors an interpretation of the symptomatology as an evidence of decreased sympathetic activity to the injured limb and a resulting upregulation of adrenergic sensitivity. The clinical use of phenoxybenzamine for the treatment of CRPS is reviewed, and mechanisms of action that include potential immunomodulatory/anti-inflammatory effects are presented. Also, a recent study identified phenoxybenzamine as a potential intervention for pain mediation from its effects on gene expression in human cell lines; on this basis, it was tested and found to be capable of reducing pain behavior in a classical animal model of chronic pain.

Rapid point-of-care assay of enoxaparin anticoagulant efficacy in whole blood.

There is the need for a clinical assay to determine the extent to which a patient's blood is effectively anticoagulated by the low-molecular-weight-heparin (LMWH), enoxaparin. There are also urgent clinical situations where it would be important if this could be determined rapidly. The present assay is designed to accomplish this. We only assayed human blood samples that were spiked with known concentrations of enoxaparin. The essential feature of the present assay is the quantification of the efficacy of enoxaparin in a patient's blood sample by degrading it to complete inactivity with heparinase. Two blood samples were drawn into Vacutainer tubes (Becton-Dickenson; Franklin Lakes, NJ) that were spiked with enoxaparin; one sample was digested with heparinase for 5 min at 37 °C, the other sample represented the patient's baseline anticoagulated status. The percent shortening of clotting time in the heparinase-treated sample, as compared to the baseline state, yielded the anticoagulant contribution of enoxaparin. We used the portable, battery operated Hemochron 801 apparatus for measurements of clotting times (International Technidyne Corp., Edison, NJ). The apparatus has 2 thermostatically controlled (37 °C) assay tube wells. We conducted the assays in two types of assay cartridges that are available from the manufacturer of the instrument. One cartridge was modified to increase its sensitivity. We removed the kaolin from the FTK-ACT cartridge by extensive rinsing with distilled water, leaving only the glass surface of the tube, and perhaps the detection magnet, as activators. We called this our minimally activated assay (MAA). The use of a minimally activated assay has been studied by us and others. (2-4) The second cartridge that was studied was an activated partial thromboplastin time (aPTT) assay (A104). This was used as supplied from the manufacturer. The thermostated wells of the instrument were used for both the heparinase digestion and coagulation assays. The assay can be completed within 10 min. The MAA assay showed robust changes in clotting time after heparinase digestion of enoxaparin over a typical clinical concentration range. At 0.2 anti-Xa I.U. of enoxaparin per ml of blood sample, heparinase digestion caused an average decrease of 9.8% (20.4 sec) in clotting time; at 1.0 I.U. per ml of enoxaparin there was a 41.4% decrease (148.8 sec). This report only presents the experimental application of the assay; its value in a clinical setting must still be established.

Toward development of a point-of-care assay of enoxaparin anticoagulant activity in whole blood.

There is need for a rapid assay to determine the efficacy of low-molecular-weight-heparin (LMWH) in whole blood. Heparinase was used to eliminate, and thereby quantify, the anticoagulant activity of the low-molecular-weight-heparin, enoxaparin. The percent change in the clotting time of whole blood in the presence of heparinase yielded the anticoagulant contribution of enoxaparin. A minimally activated assay (MAA) of whole blood clotting time was evaluated for the detection and relative quantification of enoxaparin. The assay cartridge consisted of a plain glass tube and detection magnet, with no additional sources of activation. Comparisons were also made with a point-of-care, activated partial thromboplastin time (aPTT) assay. Plasma or whole blood was spiked with enoxaparin at concentrations ranging from 0.1 to 1.0 anti-factor Xa IU/ml. A commercial preparation of heparinase I was used to digest enoxaparin, and clotting times were determined with and without heparinase incubation. Heparinase digestion caused an average shortening of clotting time of 21.1% (47.3 s) in blood spiked with 0.4 anti-Xa IU/ml enoxaparin, an amount expected in the therapeutic range; also, 0.1 anti-Xa IU/ml of enoxaparin could be reliably detected. The assay performed comparably when transferred to a point-of-care setting with heparinase being added directly to citrated blood collection tubes, followed by either MAA or aPTT assay. Strong correlations were obtained with both assays between the percent change in clotting time (after heparinase) and the added concentration of enoxaparin, or in comparison with the chromogenically measured concentration of enoxaparin. The assays for an individual blood sample can be completed within 10 min.

Experience (mostly negative) with the use of sympathomimetic agents for weight loss.

Sympathomimetic agents have a poor history of long-term success in the treatment of obesity. From earlier experiences with amphetamine and its analogs, to more recent drugs with direct effects on adrenergic receptors or indirect effects from release of catecholamines or inhibition of reuptake, cardiovascular toxicity (strokes and cardiac arrhythmias) has been the major concern. These concerns also extended to food supplements containing ephedra alkaloids and may require consideration for current supplements containing the sympathomimetic drug, synephrine.

Increased risk of general anesthesia for high-risk patients undergoing magnetic resonance imaging.

OBJECTIVE: The aim of this study was to review mortality rate pertinent to anesthesia in magnetic resonance imaging (MRI) settings and compare it with operating room (OR) mortality rate. MATERIALS AND METHODS: A total of 47,389 anesthetics have been administered to pediatric patients in the Montefiore Medical Center between February 1998 and September 2007, of which 11,700 (25%) were administered for procedures performed outside the OR. Our data collection system allows us to separate outside OR locations into 2 separate groups. One group includes MRI, computed tomography scan, and radiology, and the other includes gastrointestinal procedures, hematology-oncology, and all others. The data we present show the total number of cases, and demographic numbers reflect the total numbers as well. RESULTS: On the basis of the 3 deaths from general anesthesia occurring in the MRI suite, the resulting non-OR mortality rate at our institution was approximately 1 in 3900. Comparatively, in the same period, our mortality rate for procedures performed intraoperatively under general anesthesia was 1 in 7138. Therefore, there is almost a 2-fold increased risk in mortality associated with non-OR versus OR anesthetics at our institution. CONCLUSION: Our analysis shows that the administration of anesthesia in MRI suite possesses inherent risks that might be the same or even higher than those in the OR. BACKGROUND: Over the last 2 decades, the scope of anesthesia practice has expanded to include remote sites away from the operating room. As the number of diagnostic and therapeutic interventions performed outside the operating room continues to increase, anesthesiologists are being faced with challenges of providing care for more medically complex patients while adapting to fewer resources, with lack of support system commonly available in the operating room. In this article, we present three pediatric cases resulting in poor outcomes, all of which occurred in our MRI suite.

Treatment of complex regional pain syndrome type I with oral phenoxybenzamine: rationale and case reports.

The nonselective alpha-adrenergic antagonist, phenoxybenzamine, has been used in the treatment of neuropathic pain syndromes, specifically, complex regional pain syndrome (CRPS) types I and II. This agent has also previously been used in intravenous regional peripheral blocks for treatment of CRPS I; however, an intravenous preparation of phenoxybenzamine is not currently available in the U.S.A. In this case series, systemic administration was more appropriate for three of the four patients, as their syndromes had spread beyond the initial area of surgery or trauma. We report an apparent clinical benefit in three of the four patients following oral administration. We postulate that this may be due to the noncompetitive (irreversible) blockade of alpha(1)- and alpha(2)-adrenergic receptors. We further hypothesize that this blockade could reduce stimulation of an increased population of adrenergic receptors in hyperalgesic skin, blunt the stimulation by norepinephrine of alpha(2)-adrenergic receptors on macrophages, and ultimately reduce the release of proinflammatory cytokines from cellular elements.

Minimizing tolerance and withdrawal to prolonged pediatric sedation: case report and review of the literature.

Midazolam and fentanyl infusions are commonly used for prolonged sedation and analgesia in the pediatric intensive care setting. Tolerance and withdrawal are major concerns when these infusions are used for days or weeks. Here, we review the current approaches to prolonged pediatric sedation using midazolam and fentanyl and discuss newer strategies to avoid tolerance and withdrawal syndromes. We report the case of a pediatric burn patient who developed tolerance syndrome and a movement disorder in our institution. We also review the relevant literature and methods of minimizing tolerance and withdrawal. Prolonged sedation is often necessary in treating critically ill children, and tolerance and abstinence syndrome can complicate a successful recovery. Scoring systems can be used to minimize oversedation and to titrate effectively. "Drug cycling," "wake-up protocols," and weaning regimens, possibly combined with adjuvant drugs, are being implemented successfully. Such novel approaches may decrease the incidence of tolerance and withdrawal associated with prolonged sedative and analgesic use.

Accuracy of pharmacokinetic models for predicting plasma fentanyl concentrations in lean and obese surgical patients: derivation of dosing weight ("pharmacokinetic mass").

BACKGROUND: The currently available pharmacokinetic models for fentanyl were derived from normal weight patients and were not scaled to body weight. Their application to obese patients may cause overprediction of the plasma concentration of fentanyl. This study examined the influence of body weight on the predictive accuracy of two models (Anesthesiology 1990; 73:1091-102 and J Pharmacol Exp Ther 1987; 240:159-66). Further, we attempted to derive suggested dosing mass weights for fentanyl that improved predicted accuracy. METHOD: Seventy patients undergoing major elective surgery with total body weight (TBW) <85 kg and body mass index <30 (Group L) and 39 patients with TBW >/=85 kg and body mass index >30 (Group O) were studied. In Group L and Group O, the mean TBW was 69 kg, and 125 kg, respectively and the mean body mass index in Group L and Group O was 24 and 44, respectively. Fentanyl infusion was used during surgery and postoperatively for analgesia. Plasma fentanyl concentrations were measured and predicted concentrations were obtained by computer simulation; 465 pairs of measured and predicted values were obtained. RESULTS: The influence of TBW on the performance errors of the original two models was examined with nonlinear regression analysis. Shafer error versus TBW showed a highly significant negative relationship (R squared = 0.689, P < 0.001); i.e., the Shafer model systematically overestimated fentanyl concentration as weight increased. The Scott and Stanski model showed greater variation (R squared = 0.303). We used the exponential equation for Shafer performance error versus TBW to derive suggested dosing weights ("pharmacokinetic mass") for obese patients. The pharmacokinetic mass versus TBW curve was essentially linear below 100 kg (with slope of 0.65) and approached a plateau above 140 kg. For patients weighing 140 to 200 kg, dosing weights of 100-108 kg are projected. Total body clearance (ml/min) showed a strong linear correlation with pharmacokinetic mass (r = 0.793; P < 0.001), whereas the relationship with TBW was nonlinear. CONCLUSION: Actual body weight overestimates fentanyl dose requirements in obese patients. Dosing weight (pharmacokinetic mass) derived from the nonlinear relationship between prediction error and TBW proved to have a linear relationship with clearance.

The effect of preoperative antiplatelet/anticoagulant prophylaxis on postoperative blood loss in cardiac surgery.

UNLABELLED: In this study we sought to determine whether preoperative treatment with antiplatelet and/or anticoagulant drugs influences postoperative blood loss after coronary artery bypass graft surgery. Although prophylactic treatment to prevent ischemic events preoperatively is often necessary, the treatment frequently continues until there may be a risk of increased bleeding (i.e., within 5-7 days before surgery). With patient consent, a preincision blood sample was collected prospectively from 93 adult subjects who presented randomly. They consisted of 3 groups regarding their primary preoperative regimen: 1) no preoperative treatment within the week before surgery; 2) platelet adenosine diphosphate (ADP) receptor antagonist; 3) ADP receptor antagonist plus IV heparin. Postoperative chest tube drainage (24 h) in the group that received ADP antagonist alone was more (P < 0.05) than either of the other groups: 503 +/- 56; 633 +/- 55; 439 +/- 29 mL (mean +/- SEM) for Groups 1, 2, and 3, respectively. Combined treatment with ADP antagonist plus heparin infusion appeared to prevent the increased blood loss with the ADP antagonist alone. Preincision and postoperative plasma fibrinogen concentrations were largest (P < 0.05) in the group that received the combination treatment; mean +/- SEM for groups 1, 2, and 3 preincision, 311 +/- 17, 366 +/- 16, and 423 +/- 18 mg/dL, and postoperatively, 229 +/- 16, 267 +/- 13, and 312 +/- 16 mg/dL. Postoperative fibrinogen showed strong dependence on preoperative fibrinogen in all groups (r = 0.576 to 0.825; P = 0.01 to 10(-6)). Prevention of the increased blood loss in the ADP receptor antagonist group by the addition of a heparin infusion may have been attributable to a conservation of coagulation factors, as evidenced by the increased plasma fibrinogen concentrations with combined prophylactic treatment. IMPLICATIONS: The objective of this study was to determine whether preoperative treatment with antiplatelet and/or anticoagulant drugs influences the extent of blood loss in the 24-h period after cardiac surgery.

Efficacy of short-course ceftriaxone therapy for Borrelia burgdorferi infection in C3H mice.

Ceftriaxone is highly effective clinically in patients with Lyme disease. We studied a representative invasive human isolate of Borrelia burgdorferi for which the MBC of ceftriaxone was 0.050 microg/ml. A once-per-day dosage regimen of ceftriaxone (50 mg/kg/dose) administered intramuscularly for 5 days was 100% effective in sterilizing tissue samples of C3H mice infected with this strain of B. burgdorferi, regardless of whether the mice were being treated concomitantly with a corticosteroid. Administration of the same five doses of ceftriaxone at 6-h intervals over just 24 h was also 100% effective. These experiments suggest that shorter courses of antibiotics than those currently recommended should be considered for study in patients with early uncomplicated Lyme disease.