Frequency and Characteristics of Postoperative Neuropathy in Individuals on Gender-Affirming Hormone Therapy Undergoing Gender Affirmation Surgery: A Retrospective Cohort Study.

Introduction Gender affirmation surgery includes procedures of the face, larynx, chest, reproductive system, external genitalia, and adipose tissue performed to ameliorate incongruence between gender identity and phenotype. The annual number of gender affirmation surgeries performed in the United States has increased significantly. There have been no investigations into the frequency of peripheral neuropathy after gender affirmation surgery, which is an important topic, given transgender individuals are at increased risk for delaying necessary medical care. After appreciating a number of cases of postoperative neuropathy in our clinical practice, we hypothesized that gender affirmation surgery is a high-risk procedure for postoperative neuropathy.  Methods We conducted a one-year, monocentric, retrospective cohort study utilizing clinical data of individuals on gender-affirming hormone therapy undergoing gender-affirmation surgery under general anesthesia. The study included transgender women, assigned male at birth, receiving antiandrogen, progesterone, or estrogen therapy (target range plasma estradiol concentration 90-200 pg/ml) and transgender men, assigned female at birth, receiving antiestrogen or testosterone therapy (target range plasma testosterone concentration 320-1000 ng/dl). The primary objective was to estimate the incidence of postoperative peripheral neuropathy, defined as new numbness, paresthesia, neuropathic pain, or muscle weakness occurring in a peripheral innervation territory. Secondary objectives were to summarize the clinical presentation of neuropathy and investigate for associations between procedure characteristics and neuropathy. Results We identified nine cases of postoperative peripheral nerve injury in 232 consecutive gender affirmation procedures establishing an incidence of 3.9%. All injuries were associated with surgery longer than six hours and were characterized by sensory deficits including numbness 89% (8/9) and tingling 56% (5/9), which were diagnosed by postoperative day one. Conclusions Our results suggest that gender affirmation surgery is a high-risk procedure for postoperative neuropathy, with an incidence similar to other high-risk procedures, and an incidence that is higher than the general surgical population. However, given this has not been previously reported and our study includes a heterogenous population from a single institution, our results should be considered hypothesis generating. Additional studies that include multiple institutions are needed to confirm our findings and identify modifiable risk factors for postoperative neuropathy.

Optimizing Reversal of Neuromuscular Block in Older Adults: Sugammadex or Neostigmine.

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery.

Limited English proficiency in the labor and delivery unit.

PURPOSE OF REVIEW: Limited English proficiency (LEP) impacts patient access to safe and comprehensive care during the antepartum, intrapartum, and postpartum periods. In this review, we explore disparities in care delivery and outcomes that LEP women experience, and discuss the importance of providing language concordant care and using interpretation services appropriately. RECENT FINDINGS: The number of individuals with LEP is steadily increasing in the United States. Pregnant women with LEP suffer disparities in obstetric care and are at risk for postpartum depression, breastfeeding difficulties, and substandard newborn care after neonatal ICU discharge because of insufficient education. Addressing these issues requires the implementation of language concordant care and education, along with the utilization of medically trained interpreters. Although further evidence is needed, the authors support these interventions to improve patient satisfaction, decrease medical errors, and curtail misdiagnoses. SUMMARY: The pregnant woman with limited English proficiency is at risk of receiving suboptimal care and experiencing negative outcomes during the antepartum, intrapartum, and postpartum periods. The use of medically trained interpreters and the provision of language concordant care, through workforce diversification and the creation of forms and educational materials in diverse languages, can improve patient safety, outcomes, and quality of care.

Pharmacokinetics and Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery.

BACKGROUND: Intraperitoneal chloroprocaine has been used during cesarean delivery to supplement suboptimal neuraxial anesthesia for decades. The short in vitro half-life of chloroprocaine (11-21 seconds) has been cited to support the safety of this approach. However, there are no data regarding the rate of absorption, representing patient drug exposure, through this route of administration. Accordingly, we designed a study to determine the in vivo half-life of intraperitoneal chloroprocaine and assess clinical tolerability. METHODS: We designed a single-center, prospective, cohort, multiple-dose escalation study of women 18 to 50 years of age undergoing cesarean delivery with spinal anesthesia. Chloroprocaine (40 mL) was administered after delivery of the newborn and before uterine closure. The first cohort (n = 5) received 1%, the second cohort (n = 5) received 2%, and the third cohort (n = 5) received 3% chloroprocaine solution. Maternal blood samples were obtained before administration and 1, 5, 10, 20, and 30 minutes after dosing. The primary objective was to define the pharmacokinetic profile of intraperitoneal chloroprocaine, including in vivo half-life. The secondary objective was to evaluate tolerability through determination of peak plasma concentration and prospective assessment for local anesthetic systemic toxicity. RESULTS: The peak plasma concentration occurred 5 minutes after intraperitoneal administration in all 3 cohorts: 64.8 ng/mL (6.5 µg/kg), 28.7 ng/mL (2.9 µg/kg), and 799.2 ng/mL (79.9 µg/kg) for 1%, 2%, and 3% chloroprocaine, respectively. The in vivo half-life of chloroprocaine after intraperitoneal administration was estimated to be 5.3 minutes (95% confidence interval, 4.0-6.6). We did not detect clinical signs of local anesthetic systemic toxicity in any of the 3 cohorts. CONCLUSIONS: The in vivo half-life of intraperitoneal chloroprocaine (5.3 minutes) is more than an order of magnitude greater than the in vitro half-life (11-21 seconds). However, maximum plasma concentrations of chloroprocaine (C max range, 0.05-79.9 µg/kg) were not associated with local anesthetic systemic toxicity and remain well below our predefined safe level of exposure (970 µg/kg) and levels associated with clinical symptoms (2.6-2.9 mg/kg). Therefore, our study suggests that intraperitoneal chloroprocaine, in a dosage ≤1200 mg, administered after fetal extraction, is well tolerated during cesarean delivery.

Diagnosis and Management of Obesity Hypoventilation Syndrome during Labor.

Obesity hypoventilation syndrome (OHS) is a disorder in which patients with a body mass index ≥30 kg/m2 develop awake hypercapnia with a partial pressure of carbon dioxide ≥45 mm Hg, in the absence of other diseases that may produce alveolar hypoventilation. Additional clinical features include sleep disordered breathing, restrictive lung disease, polycythemia, hypoxemia, and an increased serum bicarbonate concentration (≥27 mEq/L). Anesthesia providers should be familiar with OHS because it is often undiagnosed, it is associated with a higher mortality rate than obstructive sleep apnea, and it is projected to increase in prevalence along with the obesity epidemic. In this case, a 33-year-old obese woman with presumed OHS developed respiratory acidosis during induction of labor. Continuous positive airway pressure treatment was initiated, but the patient continued to have hypercapnia. A cesarean delivery was recommended. The patient had baseline orthopnea due to her body habitus; thus, despite adequate labor analgesia, a cesarean delivery was completed with general endotracheal anesthesia. We believe this patient had OHS despite a serum bicarbonate <27 mEq/L, a partial pressure of oxygen >70 mm Hg, and a hemoglobin <16 g/dL, which would typically rule out OHS. Pregnant women experience a decrease in serum bicarbonate concentration due to progesterone-mediated hyperventilation, an increase in arterial oxygenation from increased minute ventilation and higher cardiac output, and a decrease in hemoglobin due to the physiologic anemia of pregnancy. Thus, OHS may be defined differently in pregnant than in non-pregnant patients.

Delivery and neuraxial technique outcomes in patients with hemophilia and in hemophilia carriers: a systematic review.

Female carriers are more common than males with hemophilia and unrecognized factor VIII or IX deficiency is associated with intrauterine growth retardation, epidural hematomas, blood transfusion, and peripartum hemorrhage. A review was conducted to assess the evidence for professional society recommendations for > 50% factor levels during labor. Two searches of Pubmed, CINAHL, Cochrane, and Google Scholar were completed in October 2019. The first for case reports and series described neuraxial techniques in patients with hemophilia-regardless of sex, age, or pregnant status. The second for case reports and series described bleeding outcomes of parturients with hemophilia. Primary outcomes were diagnosis of neuraxial hematoma (first search) and postpartum bleeding complications (second search). Thirteen articles (n = 134) described neuraxial techniques in patients with hemophilia. Neuraxial hematoma with paraplegia occurred in 3/134 patients-all had a factor level of 1%. Nineteen articles (2712 deliveries in 2657 women) described bleeding outcomes. Postpartum hemorrhage occurred in 7.1% (193/2712) of deliveries, of which 60% necessitated blood transfusion. Postpartum bleeding complications were twice as likely (51.0% [25/49] vs. 25.6% [52/203], P < 0.001) with factor activity < 50%. Therefore, factor levels should be assessed and increased above 50% prior to neuraxial technique and delivery.Trial registration: PROSPERO 2018 CRD42018110215.

Randomised controlled trial of sugammadex or neostigmine for reversal of neuromuscular block on the incidence of pulmonary complications in older adults undergoing prolonged surgery.

BACKGROUND: Residual neuromuscular block has been associated with postoperative pulmonary complications. We hypothesised that sugammadex reduces postoperative pulmonary complications in patients aged ≥70 yr having surgery ≥3 h, compared with neostigmine. METHODS: Patients were enrolled in an open-label, assessor-blinded, randomised, controlled trial. At surgical closure, subjects were equally randomised to receive sugammadex 2 mg kg-1 or neostigmine 0.07 mg kg-1 (maximum 5 mg) for rocuronium reversal. The primary endpoint was incidence of postoperative pulmonary complications. Secondary endpoints included residual paralysis (train-of-four ratio <0.9 in the PACU) and Phase 1 recovery (time to attain pain control and stable respiratory, haemodynamic, and neurological status). The analysis was by intention-to-treat. RESULTS: Of the 200 subjects randomised, 98 received sugammadex and 99 received neostigmine. There was no significant difference in the primary endpoint of postoperative pulmonary complications despite a signal towards reduced incidence for sugammadex (33% vs 40%; odds ratio [OR]=0.74; 95% confidence interval [CI]=[0.40, 1.37]; P=0.30) compared with neostigmine. Sugammadex decreased residual neuromuscular block (10% vs 49%; OR=0.11, 95% CI=[0.04, 0.25]; P<0.001). Phase 1 recovery time was comparable between sugammadex (97.3 min [standard deviation, sd=54.3]) and neostigmine (110.0 min [sd=62.0]), difference -12.7 min (95% CI, [-29.2, 3.9], P=0.13). In an exploratory analysis, there were fewer 30 day hospital readmissions in the sugammadex group compared with the neostigmine group (5% vs 15%; OR=0.30, 95% CI=[0.08, 0.91]; P=0.03). CONCLUSIONS: In older adults undergoing prolonged surgery, sugammadex was associated with a 40% reduction in residual neuromuscular block, a 10% reduction in 30 day hospital readmission rate, but no difference in the occurrence of postoperative pulmonary complications. Based on this exploratory study, larger studies should determine whether sugammadex may reduce postoperative pulmonary complications and 30 day hospital readmissions. CLINICAL TRIAL REGISTRATION: NCT02861131.

Education Program Regarding Labor Epidurals Increases Utilization by Hispanic Medicaid Beneficiaries: A Randomized Controlled Trial.

BACKGROUND: Hispanic women choose epidural labor analgesia less commonly than non-Hispanic women. This may represent a healthcare disparity related to a language barrier and inadequate opportunities for labor analgesia education. It was hypothesized that a language-concordant, educational program regarding labor epidurals would improve epidural utilization in two independent cohorts of Hispanic and non-Hispanic women. METHODS: A randomized controlled trial, blinded to anesthesia, nursing, and obstetric providers, was completed at an academic hospital (February 2015 to February 2017). Two cohorts of Medicaid beneficiaries of Hispanic (English- and/or Spanish-speaking) and non-Hispanic ethnicity were enrolled concurrently. The patients were randomized to routine care alone or routine care and an additional educational program comprised of three components: a video show, corresponding pamphlet, and in-person counseling. The primary endpoint was use of epidural labor analgesia. The secondary endpoint was change in response before and after delivery on common misconceptions based on a 12-point epidural questionnaire. RESULTS: Hispanic women randomized to the intervention group were 33% more likely to choose epidural analgesia compared to the routine care group (40 of 50 [80%] vs. 30 of 50 [60%]; risk ratio, 1.33 [95% CI, 1.02 to 1.74]; P = 0.029). For the non-Hispanic cohort, no difference was detected in epidural use between the intervention and routine care groups (41 of 50 [82%] vs. 42 of 49 [86%]; risk ratio, 0.96 [95% CI, 0.80 to 1.14]; P = 0.62), but the study was underpowered to determine a result of no difference. Patients assigned to the intervention had a greater improvement in epidural understanding compared with routine care, among both Hispanic (2.26 vs. 0.74, respectively; difference in change from baseline, 1.52 [95% CI, 0.77 to 2.27]; P < 0.001) and non-Hispanic (1.36 vs. 0.33, respectively; difference in change from baseline, 1.03 [95% CI, 0.23 to 1.75]; P = 0.005) cohorts. There were no adverse events during the trial. CONCLUSIONS: The educational program increased epidural use among Hispanic women. The educational program reduced misconceptions regarding epidural analgesia in both Hispanic and non-Hispanic cohorts.

Assessment of blood-brain barrier integrity and neuroinflammation in preeclampsia.

BACKGROUND: Although blood-brain barrier integrity is intact under normal pregnancy conditions, animal studies suggest that blood-brain barrier impairment occurs in preeclampsia. Yet, human data are limited, and the integrity of the blood-brain barrier has not been assessed in women with preeclampsia. OBJECTIVE: We sought to test the hypothesis that the integrity of the blood-brain barrier is impaired and that neuroinflammation is increased in women with preeclampsia. STUDY DESIGN: We performed an observational case-control study in pregnant women >24 weeks gestation who underwent spinal anesthesia for elective cesarean delivery or combined spinal epidural analgesia for labor. Cases were women with preeclampsia, and control subjects were women with either healthy pregnancy, chronic hypertension, or gestational hypertension. Paired samples of blood, urine, and cerebrospinal fluid were collected from each subject before delivery. We measured albumin, C5a, C5b-9, tumor necrosis factor-α, and interleukin-6 concentrations in plasma and cerebrospinal fluid, and albumin, C5a, and C5b-9 concentrations in urine, using colorimetric or enzyme-linked immunosorbent assays. The ratio of albumin in cerebrospinal fluid to plasma (Qalb) was used as a surrogate for maternal blood-brain barrier integrity. Cerebrospinal fluid concentrations of C5a, C5b-9, tumor necrosis factor-α, and interleukin-6 were used as surrogate markers of neuroinflammation. Differences in Qalb and cerebrospinal fluid protein concentrations between groups were assessed by nonparametric test of medians. RESULTS: Forty-eight subjects were enrolled, which included 16 cases with preeclampsia, 16 control subjects with healthy pregnancy, and 16 control subjects with either chronic or gestational hypertension. Qalb values were not increased in preeclampsia cases compared with healthy or hypertensive control subjects (Qalb median, 3.5 [interquartile range, 2.9-5.1] vs 3.9 [interquartile range, 3.0-4.8] vs 3.9 [interquartile range, 3.0-4.8]; P=.78]. Moreover, Qalb values were not increased in the subset of women with preeclampsia with severe features (n=8) compared with those without severe features (n=8; Qalb median, 3.5 [interquartile range, 3.3-4.9] vs 3.7 [interquartile range, 2.3-5.5]; P=.62]. Cerebrospinal fluid concentrations of C5a, C5b-9, tumor necrosis factor-α and interleukin-6 were not increased in cases of preeclampsia, compared with control subjects with either healthy pregnancy, chronic hypertension, or gestational hypertension (P>.05, all comparisons). In contrast to the negative findings in cerebrospinal fluid, plasma concentrations of both C5b-9 and interleukin-6 and urine concentrations of C5a and C5b-9 were increased in cases of preeclampsia. CONCLUSION: Through measurements of albumin, complement proteins, and cytokines in paired samples of blood and cerebrospinal fluid at the time of delivery, we found no evidence of blood-brain barrier impairment or neuroinflammation in preeclampsia. Larger studies that will investigate a wider range of proteins are suggested to validate our findings.

Cardiovascular and Ventilatory Consequences of Laparoscopic Surgery.

Although laparoscopic surgery accounts for >2 million surgical procedures every year, the current preoperative risk scores and guidelines do not adequately assess the risks of laparoscopy. In general, laparoscopic procedures have a lower risk of morbidity and mortality compared with operations requiring a midline laparotomy. During laparoscopic surgery, carbon dioxide insufflation may produce significant hemodynamic and ventilatory consequences such as increased intraabdominal pressure and hypercarbia. Hemodynamic insults secondary to increased intraabdominal pressure include increased afterload and preload and decreased cardiac output, whereas ventilatory consequences include increased airway pressures, hypercarbia, and decreased pulmonary compliance. Hemodynamic effects are accentuated in patients with cardiovascular disease such as congestive heart failure, ischemic heart disease, valvular heart disease, pulmonary hypertension, and congenital heart disease. Prevention of cardiovascular complications may be accomplished through a sound understanding of the hemodynamic and physiological consequences of laparoscopic surgery as well as a defined operative plan generated by a multidisciplinary team involving the preoperative consultant, anesthesiologist, and surgeon.

Methodological quality of randomized controlled trials of postoperative epidural analgesia: validation of the Epidural Analgesia Trial Checklist as a specific instrument to evaluate methodology.

BACKGROUND: The overall benefits of epidural analgesia are controversial, in part because of the varying quality of methodology in published randomized controlled trials (RCTs). We performed a systematic review of available RCTs to examine the methodological quality of epidural analgesia trials. Current instruments for evaluating the quality of methodology are generic; thus, we also developed a specific assessment tool named Epidural Analgesia Trial Checklist (EATC). METHODS: The National Library of Medicine's PubMed database was searched (1966 to January 2006) for RCTs of epidural analgesia. All RCTs that had epidural infusion analgesia in at least 1 study arm and as primary intervention for randomization were included. Two independent reviewers were given blinded full-text paper versions of each article and reviewed all articles for inclusion in this study. Study characteristics were extracted from accepted RCTs, and reviewers completed the standardized 7-item Jadad score, 22-item Consolidated Standards of Reporting Trials (CONSORT) checklist, and 8-item EATC for evaluation of methodological quality. RESULTS: A total of 321 articles met all inclusion criteria. The overall median (first, third quartiles) Jadad, CONSORT, and EATC scores were 2 (1, 3), 10 (8, 11), and 4 (3, 6) (of maximum scores of 5, 22, and 8), respectively. For all assessments, we found significantly higher methodological study quality for articles with a larger study population size, those written by a first author affiliated with an anesthesiology department, and studies published after release of the CONSORT statement with a significant overall increase in methodological quality over time. There was no effect on methodological quality with regard to region of publication or number of centers. There was relatively high interrater agreement when using the EATC (κ = 0.92). The items most frequently lacking from the studies captured using the EATC were appropriate description/definition of adverse effects (11.8% of all studies properly reported this), proper presentation of visual analog scale (VAS) pain scores (31.2%), and assessment of VAS pain both at rest and with activity (39.9%). CONCLUSIONS: Methodology scores for epidural analgesia RCTs have improved over time. The EATC seems to correlate well with other commonly used generic assessments for methodological RCT quality and be useful for assessing methodological quality of epidural RCTs. Future epidural analgesia RCTs should focus on improving appropriate description/definition of adverse effects, proper presentation of VAS pain scores, and assessment of VAS pain both at rest and with activity.

Retinal hemorrhages and shaken baby syndrome: an evidence-based review.

BACKGROUND: Among the causes of non-accidental head injury (NAHI), shaken baby syndrome (SBS) is difficult to diagnose and is associated with retinal hemorrhages (RH). DESCRIPTION: To identify findings and patterns of RH specific to SBS, a PubMed search using the keywords "shaken baby syndrome" or "child abuse" and "retinal hemorrhage" was conducted; 66 articles met the inclusion criteria. The published data address the utility of RH in three categories: 1) in diagnosing SBS; 2) as correlated to intracranial pathology; and 3) in prognosticating SBS. The present review aimed to summarize studies in a way that facilitates clinical decision-making. RESULTS: Studies found a 53-80% incidence of RH with abusive head injury and a 0-10% incidence with proven severe accidental trauma. RHs are found bilaterally 62.5-100% of the time in SBS cases, and flame-shaped hemorrhages are the most common. The incidence of RH from convulsions, chest compressions, forceful vomiting, and severe persistent coughing in the absence of another condition known to cause RH is 0.7%, 0-2.3%, 0%, and 0%, respectively. CONCLUSION: SBS remains a difficult cause of NAHI to diagnose. Ophthalmologic examination can provide critical diagnostic and prognostic information in cases of suspected SBS. Child abuse should be highly suspect in children with RH and a parental explanation of accidental head injury, especially if the RHs are found to be bilateral, flame-shaped, or to extend through to all layers of the retina.