Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association.

Pulmonary hypertension, defined as an elevation in blood pressure in the pulmonary arteries, is associated with an increased risk of death. The prevalence of pulmonary hypertension is increasing, with an aging population, a rising prevalence of heart and lung disease, and improved pulmonary hypertension survival with targeted therapies. Patients with pulmonary hypertension frequently require noncardiac surgery, although pulmonary hypertension is associated with excess perioperative morbidity and death. This scientific statement provides guidance on the evaluation and management of pulmonary hypertension in patients undergoing noncardiac surgery. We advocate for a multistep process focused on (1) classification of pulmonary hypertension group to define the underlying pathology; (2) preoperative risk assessment that will guide surgical decision-making; (3) pulmonary hypertension optimization before surgery to reduce perioperative risk; (4) intraoperative management of pulmonary hypertension to avoid right ventricular dysfunction and to maintain cardiac output; and (5) postoperative management of pulmonary hypertension to ensure recovery from surgery. Last, this scientific statement highlights the paucity of evidence to support perioperative pulmonary hypertension management and identifies areas of uncertainty and opportunities for future investigation.

Twin-twin transfusion syndrome complicated by single ventricle physiology: A case report.

Clinically significant extrauterine twin-twin transfusion syndrome in conjoined twins is rare and carries a high risk of perinatal mortality. The ensuing postnatal imbalance in circulation across connecting vessels results in hypovolemia in the donor and hypervolemia in the recipient. Data on management and treatment are sparse especially in the setting of a single ventricle congenital heart defect. We present a case of a pair of omphalopagus conjoined twins, one with a single ventricle physiology (Twin B), who developed twin-twin transfusion syndrome shortly after birth. The resulting pathophysiology in the setting of a single ventricle congenital heart defect created added layers of complexity to their management and expedited surgical separation. Shunting from Twin B to Twin A-with an anatomically normal heart-resulted in mal-perfusion and rapid deterioration jeopardizing the health of both twins. In the preoperative course, steps taken to medically optimize the twins prior to surgery and the anesthetic considerations are detailed in this report.

An unexpected COVID-19 diagnosis during emergency surgery in a neonate.

A 4-day-old, 3.3 kg infant presented with suspected intestinal malrotation, necessitating emergent diagnostic laparoscopy. Intra-operatively, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) came back positive. This is the first case report of emergency surgery and anesthesia in a positive SARS-CoV-2 newborn. This report highlights a neonate with an incidental positive SARS-CoV-2 test, no known exposure history, negative polymerase chain reaction maternal testing, and absence of respiratory symptoms who required modified pressure control ventilation settings to adequately ventilate with the high-efficiency particulate air filter in situ.

Clinical outcomes of cardiac surgery patients undergoing therapeutic plasma exchange for heparin-induced thrombocytopenia.

BACKGROUND AND OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated condition that leads to thrombocytopenia and possible thrombosis. Patients with HIT who require cardiac surgery pose a challenge as high doses of heparin or heparin alternatives are required to permit cardiopulmonary bypass (CPB). Intraoperative therapeutic plasma exchange (TPE) is a valuable adjunct in the management of antibody-mediated syndromes including HIT. The clinical impact of TPE on thromboembolic events, bleeding and mortality after heparin re-exposure is not well established. We hypothesized that TPE with heparin re-exposure will not lead to HIT-related thromboembolic events, bleeding or increased mortality after cardiac surgery with CPB. MATERIALS AND METHODS: We reviewed 330 patients who received perioperative TPE between September 2012 and September 2017. RESULTS: Twenty four patients received TPE for HIT before anticipated heparin use for CPB. Most patients were males (79%) scheduled for advanced heart failure therapies. Three patients (12·5%) died within 30 days after surgery but none of the deaths were considered HIT-related. Thromboembolic events (TE) occurred in 3 patients within 7 days of surgery; of those, two were possibly HIT-related. CONCLUSION: Therapeutic plasma exchange with heparin re-exposure was not strongly associated with HIT-related thrombosis/death after cardiac surgery with CPB.

Heparin Induced Thrombocytopenia for the Perioperative and Critical Care Clinician.

PURPOSE OF REVIEW: This review will illustrate the importance of heparin-induced thrombocytopenia in the intraoperative and critical care settings. RECENT FINDINGS: Heparin-induced thrombocytopenia (HIT) occurs more frequently in surgical patients compared with medical patients due to the inflammatory release of platelet factor 4 and perioperative heparin exposure. Recognition of this disease requires a high index of suspicion. Diagnostic tools and therapeutic strategies have been expanded and refined in recent years. SUMMARY: HIT is a condition where antibodies against the heparin/platelet factor 4 complex interact with platelet receptors to promote platelet activation, aggregation, and thrombus formation. Our review will focus on intraoperative and postoperative considerations related to HIT to help the clinician better manage this rare but often devastating hypercoagulable disease process.

Intraoperative Provocative Testing in Patients with Obstructive Hypertrophic Cardiomyopathy Undergoing Septal Myectomy.

BACKGROUND: Resolution of left ventricular outflow tract (LVOT) obstruction predicts symptom relief postmyectomy. Intraoperative measurement of LVOT gradients thus is essential for surgical guidance. We hypothesized that (1) hypertrophic cardiomyopathy patients have lower LVOT gradients when measured intraoperatively with transesophageal echocardiography (TEE) compared with preoperative measurements with transthoracic echocardiography (TTE) and that (2) intraoperative provocative testing can help evaluate the adequacy of surgical resection. METHODS: We compared resting LVOT gradients on preoperative TTE to intraoperative TEE. We also compared intraoperative resting and provoked gradients pre- and postresection. Either isoproterenol 10 µg/kg/min or dobutamine 20 µg/kg/min was used. Patients with provoked LVOT gradients >30 mm Hg were considered for further resection based on LVOT/mitral valve morphology and clinical comorbidities. RESULTS: Of 315 patients identified, 293 patients were included in the analysis. There was a statistically significant difference between preoperative TTE and intraoperative TEE resting LVOT gradients (60.9 ± 39.4 mm Hg vs 42.0 ± 30.5 mm Hg, P < .0001). Out of 197 patients who had significant resting obstruction preoperatively, 82 (41.6%) demonstrated mild or no dynamic obstruction under general anesthesia. Provocative testing with both isoproterenol and dobutamine increased peak gradients (116.8 ± 33 mm Hg isoproterenol vs 107.5 ± 33 mm Hg dobutamine, P = .03). Post-cardiopulmonary bypass, seven patients (2.3%) had LVOT gradients > 30 mm Hg at rest, while 63 patients (21.5%) had residual gradients >30 mm Hg only with provocation. Elevated gradients, persistent systolic anterior motion of the mitral valve with near contact, and/or significant mitral regurgitation with provocative testing resulted in return to cardiopulmonary bypass in 41 patients (14%). CONCLUSIONS: Resting intraoperative TEE LVOT gradients are significantly lower than preoperative TTE gradients, with systolic anterior motion of the MV and outflow obstruction often not visualized after inducing general anesthesia. Intraoperative pharmacologic provocation can identify patients who may benefit from further surgical intervention, facilitating procedural success.

Epidural Anesthesia for Cesarean Delivery in a Parturient With Lumboperitoneal Shunt: A Case Report.

A lumboperitoneal shunt facilitates dynamic flow of cerebrospinal fluid into the peritoneum. Consequently, neuraxial technique placement in the parturient with a lumboperitoneal shunt can result in unexpected levels of blockade. We present the case of a parturient with a lumboperitoneal shunt who experienced symptoms consistent with high blockade after epidural administration of 450 mg chloroprocaine. This report emphasizes potential mechanisms for high neuraxial blockade and strategies to decrease risks in this unique patient population.

Intraoperative Administration of 4-Factor Prothrombin Complex Concentrate Reduces Blood Requirements in Cardiac Transplantation.

OBJECTIVE: Assessing the efficacy of intraoperative 4-factor prothrombin complex concentrate (4F-PCC) use in blood product utilization, time to chest closure, intensive care unit (ICU) and hospital length of stay (LOS), thromboembolic complications, renal injury and mortality in left ventricular assist device (LVAD) patients on home anticoagulation therapy with warfarin, undergoing orthotopic heart transplantation (OHT). DESIGN: Retrospective analysis of OHT patients at Tufts Medical Center from May 2013 to October 2016. SETTING: Single-institution, university hospital setting. PARTICIPANTS: Patients with preexisting LVADs who received orthotopic heart transplants (n = 74; 32 patients 4F-PCC, 42 patients no 4F-PCC). INTERVENTIONS: Warfarin reversal using 4F-PCC in patients with LVADs undergoing orthotopic heart transplantation with the 4F-PCC dosing partitioned such that one-third was given pre-CPB and two-thirds were given post-CPB. MEASUREMENTS AND MAIN RESULTS: The 4F-PCC group required less plasma (6 [IQR 4] v 1.31 [IQR 2] U, p < 0.001), cryoprecipitate (10 [IQR 10] v 7.50 [IQR 5] U, p < 0.001), and packed red blood cells (5 [IQR 4] v 2 [IQR 1.5] U, p < 0.001) and had a shorter time to chest closure (618.8 ± 111.4 v 547.9 ± 110.1 minutes, p = 0.008). There was no difference in platelet transfusion (2 [IQR 1] v 2 [IQR 1] U, p = 0.16), ICU or hospital LOS, acute kidney injury, or mortality. No thrombotic complications occurred. CONCLUSIONS: Replacing plasma with 4F-PCC to reverse preoperative warfarin anticoagulation during OHT was associated with a shorter time to chest closure and less blood product utilization, without an increase in acute kidney injury, thromboembolic complications, or death.

Increased Resistance to Flow and Ventilator Failure Secondary to Faulty CO2 Absorbent Insert Not Detected During Automated Anesthesia Machine Check: A Case Report.

Most modern anesthesia workstations provide automated checkout, which indicates the readiness of the anesthesia machine. In this case report, an anesthesia machine passed the automated machine checkout. Minutes after the induction of general anesthesia, we observed a mismatch between the selected and delivered tidal volumes in the volume auto flow mode with increased inspiratory resistance during manual ventilation. Endotracheal tube kinking, circuit obstruction, leaks, and patient-related factors were ruled out. Further investigation revealed a broken internal insert within the CO2 absorbent canister that allowed absorbent granules to cause a partial obstruction to inspiratory and expiratory flow triggering contradictory alarms. We concluded that even when the automated machine checkout indicates machine readiness, unforeseen equipment failure due to unexpected events can occur and require providers to remain vigilant.

A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2.

BACKGROUND: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery. METHODS: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity. RESULTS: Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium-based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-à-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16:1 (95% CI, 10 to 26:1) for the reversal of ketamine and 3:1 (95% CI, 2 to 5:1) for the reversal of etomidate. CONCLUSIONS: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.

Acquired Muscle Weakness in the Surgical Intensive Care Unit: Nosology, Epidemiology, Diagnosis, and Prevention.

Muscle weakness is common in the surgical intensive care unit (ICU). Low muscle mass at ICU admission is a significant predictor of adverse outcomes. The consequences of ICU-acquired muscle weakness depend on the underlying mechanism. Temporary drug-induced weakness when properly managed may not affect outcome. Severe perioperative acquired weakness that is associated with adverse outcomes (prolonged mechanical ventilation, increases in ICU length of stay, and mortality) occurs with persistent (time frame: days) activation of protein degradation pathways, decreases in the drive to the skeletal muscle, and impaired muscular homeostasis. ICU-acquired muscle weakness can be prevented by early treatment of the underlying disease, goal-directed therapy, restrictive use of immobilizing medications, optimal nutrition, activating ventilatory modes, early rehabilitation, and preventive drug therapy. In this article, the authors review the nosology, epidemiology, diagnosis, and prevention of ICU-acquired weakness in surgical ICU patients.

Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents.

BACKGROUND: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. METHODS: The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine. RESULTS: In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate. CONCLUSIONS: Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.

The Surgical Optimal Mobility Score predicts mortality and length of stay in an Italian population of medical, surgical, and neurologic intensive care unit patients.

PURPOSE: We validated the Italian version of Surgical Optimal Mobility Score (SOMS) and evaluated its ability to predict intensive care unit (ICU) and hospital length of stay (LOS), and hospital mortality in a mixed population of ICU patients. MATERIALS AND METHODS: We applied the Italian version of SOMS in a consecutive series of prospectively enrolled, adult ICU patients. Surgical Optimal Mobility Score level was assessed twice a day by ICU nurses and twice a week by an expert mobility team. Zero-truncated Poisson regression was used to identify predictors for ICU and hospital LOS, and logistic regression for hospital mortality. All models were adjusted for potential confounders. RESULTS: Of 98 patients recruited, 19 (19.4%) died in hospital, of whom 17 without and 2 with improved mobility level achieved during the ICU stay. SOMS improvement was independently associated with lower hospital mortality (odds ratio, 0.07; 95% confidence interval [CI], 0.01-0.42) but increased hospital LOS (odds ratio, 1.21; 95% CI: 1.10-1.33). A higher first-morning SOMS on ICU admission, indicating better mobility, was associated with lower ICU and hospital LOS (rate ratios, 0.89 [95% CI, 0.80-0.99] and 0.84 [95% CI, 0.79-0.89], respectively). CONCLUSIONS: The first-morning SOMS on ICU admission predicted ICU and hospital LOS in a mixed population of ICU patients. SOMS improvement was associated with reduced hospital mortality but increased hospital LOS, suggesting the need of optimizing hospital trajectories after ICU discharge.

Investigation of central nervous system dysfunction in chronic pelvic pain using magnetic resonance spectroscopy and noninvasive brain stimulation.

BACKGROUND: Recent studies demonstrate that chronic pelvic pain is associated with altered afferent sensory input resulting in maladaptive changes in the neural circuitry of pain. To better understand the central changes associated with chronic pelvic pain, we investigated the contributions of critical pain-related neural circuits using single-voxel proton magnetic resonance spectroscopy (MRS) and transcranial direct current stimulation (tDCS). METHODS: We measured concentrations of neural metabolites in 4 regions of interest (thalamus, anterior cingulate cortex, primary motor, and occipital cortex [control]) at baseline and after 10 days of active or sham tDCS in patients with chronic pelvic pain. We then compared our results to those observed in healthy controls, matched by age and gender. RESULTS: We observed a significant increase in pain thresholds after active tDCS compared with sham conditions. There was a correlation between metabolite concentrations at baseline and quantitative sensory assessments. Chronic pelvic pain patients had significantly lower levels of NAA/Cr in the primary motor cortex compared with healthy patients. CONCLUSIONS: tDCS increases pain thresholds in patients with chronic pelvic pain. Biochemical changes in pain-related neural circuits are associated with pain levels as measured by objective pain testing. These findings support the further investigation of targeted cortical neuromodulatory interventions for chronic pelvic pain.

Residual Paralysis: Does it Influence Outcome After Ambulatory Surgery?

Neuromuscular blocking agents are used to facilitate tracheal intubation in patients undergoing ambulatory surgery. The use of high-dose neuromuscular blocking agents to achieve muscle paralysis throughout the case carries an increased risk of residual post-operative neuromuscular blockade, which is associated with increased respiratory morbidity. Visually monitoring the train-of-four (TOF) fade is not sensitive enough to detect a TOF fade between 0.4 and 0.9. A ratio <0.9 indicates inadequate recovery. Quantitative neuromuscular transmission monitoring (e.g., acceleromyography) should be used to exclude residual neuromuscular blockade at the end of the case. Residual neuromuscular blockade needs to be reversed with neostigmine, but it's use must be guided by TOF monitoring results since deep block cannot be reversed, and neostigmine administration after complete recovery of the TOF-ratio can induce muscle weakness. The development and use of new selectively binding reversal agents (sugammadex and calabadion) warrants reevaluation of this area of clinical practice.

Targeted therapies using electrical and magnetic neural stimulation for the treatment of chronic pain in spinal cord injury.

BACKGROUND: Chronic neuropathic pain is one of the most common and disabling symptoms in individuals with spinal cord injury (SCI). Over two-thirds of subjects with SCI suffer from chronic pain influencing quality of life, rehabilitation, and recovery. Given the refractoriness of chronic pain to most pharmacological treatments, the majority of individuals with SCI report worsening of this condition over time. Moreover, only 4-6% of patients in this cohort report improvement. Novel treatments targeting mechanisms associated with pain-maladaptive plasticity, such as electromagnetic neural stimulation, may be desirable to improve outcomes. To date, few, small clinical trials have assessed the effects of invasive and noninvasive nervous system stimulation on pain after SCI. OBJECTIVE: We aimed to review initial efficacy, safety and potential predictors of response by assessing the effects of neural stimulation techniques to treat SCI pain. SEARCH STRATEGY: A literature search was performed using the PubMed database including studies using the following targeted stimulation strategies: transcranial Direct Current Stimulation (tDCS), High Definition tDCS (HD-tDCS), repetitive Transcranial Magnetical Stimulation (rTMS), Cranial Electrotherapy Stimulation (CES), Transcutaneous Electrical Nerve Stimulation (TENS), Spinal Cord Stimulation (SCS) and Motor Cortex Stimulation (MCS), published prior to June of 2012. We included studies from 1998 to 2012. RESULTS: Eight clinical trials and one naturalistic observational study (nine studies in total) met the inclusion criteria. Among the clinical trials, three studies assessed the effects of tDCS, two of CES, two of rTMS and one of TENS. The naturalistic study investigated the analgesic effects of SCS. No clinical trials for epidural motor cortex stimulation (MCS) or HD-tDCS were found. Parameters of stimulation and also clinical characteristics varied significantly across studies. Three out of eight studies showed larger effects sizes (0.73, 0.88 and 1.86 respectively) for pain reduction. Classical neuropathic pain symptoms such as dysesthesia (defined as an unpleasant burning sensation in response to touch), allodynia (pain due to a non-painful stimulus), pain in paroxysms, location of SCI in thoracic and lumbar segments and pain in the lower limbs seem to be associated with a positive response to neural stimulation. No significant adverse effects were reported in these studies. CONCLUSIONS: Chronic pain in SCI is disabling and resistant to common pharmacologic approaches. Electrical and magnetic neural stimulation techniques have been developed to offer a potential tool in the management of these patients. Although some of these techniques are associated with large standardized mean differences to reduce pain, we found an important variability in these results across studies. There is a clear need for the development of methods to decrease treatment variability and increase response to neural stimulation for pain treatment. We discuss potential methods such as neuroimaging or EEG-guided neural stimulation and the development of better surrogate markers of response such as TMS-indexed cortical plasticity.

Etomidate and Ketamine: Residual Motor and Adrenal Dysfunction that Persist beyond Recovery from Loss of Righting Reflex in Rats.

We tested the hypothesis that etomidate and ketamine produce residual effects that modify functional mobility (measured by the balance beam test) and adrenal function (adrenocorticotropic hormone (ACTH) stimulation) immediately following recovery from loss of righting reflex in rats. Intravenous etomidate or ketamine was administered in a randomized, crossover fashion (2 or 4 mg/kg and 20 or 40 mg/kg, respectively) on eight consecutive days. Following recovery of righting reflex, animals were assessed for residual effects on functional mobility on the balance beam, motor behavior in the open field and adrenal function through ACTH stimulation. We evaluated the consequences of the effects of the anesthetic agent-induced motor behavior on functional mobility. On the balance beam, etomidate-treated rats maintained their grip longer than ketamine-treated rats, indicating greater balance abilities (mean ± SD, 21.5 ± 25.1 s vs. 3.0 ± 4.3 s respectively, p < 0.021). In the open field test, both dosages of etomidate and ketamine had opposite effects on travel behavior, showing ketamine-induced hyperlocomotion and etomidate-induced hypolocomotion. There was a significant interaction between anesthetic agent and motor behavior effects for functional mobility effects (p < 0.001). Corticosterone levels were lower after both 40 mg/kg ketamine and 4 mg/kg etomidate anesthesia compared to placebo, an effect stronger with etomidate than ketamine (p < 0.001). Following recovery from anesthesia, etomidate and ketamine have substantial side effects. Ketamine-induced hyperlocomotion with 20 and 40 mg/kg has stronger effects on functional mobility than etomidate-induced hypolocomotion with 2 and 4 mg/kg. Etomidate (4 mg/kg) has stronger adrenal suppression effects than ketamine (40 mg/kg).