Optimization of kidney function in cardiac surgery patients with intra-abdominal hypertension: expert opinion.

Cardiac surgery-associated acute kidney injury (CSA-AKI) affects up to 42% of cardiac surgery patients. CSA-AKI is multifactorial, with low abdominal perfusion pressure often overlooked. Abdominal perfusion pressure is calculated as mean arterial pressure minus intra-abdominal pressure (IAP). IAH decreases cardiac output and compresses the renal vasculature and renal parenchyma. Recent studies have highlighted the frequent occurrence of IAH in cardiac surgery patients and have linked the role of low perfusion pressure to the occurrence of AKI. This review and expert opinion illustrate current evidence on the pathophysiology, diagnosis, and therapy of IAH and ACS in the context of AKI.

Continuous Urine Output-Based Alert Identifies Cardiac Surgery-associated Acute Kidney Injury Earlier Than Serum Creatinine: A Prospective and Retrospective Observational Study.

OBJECTIVE(S): Acute kidney injury (AKI) is defined and staged by reduced urine output (UO) and increased serum creatinine (SCr). UO is typically measured manually and documented in the electronic health record, making early and reliable detection of oliguria-based AKI and electronic data extraction challenging. The authors investigated the diagnostic performance of continuous UO, enabled by active drain line clearance-based alerts (Accuryn AKI Alert), compared with AKI stage 2 SCr criteria and their associations with length of stay, need for continuous renal replacement therapy, and 30-day mortality. DESIGN: This study was a prospective and retrospective observational study. SETTING: Nine tertiary centers participated. PARTICIPANTS: Cardiac surgery patients were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 522 patients were analyzed. AKI stages 1, 2, and 3 were diagnosed in 32.18%, 30.46%, and 3.64% of patients based on UO, compared with 33.72%, 4.60%, and 3.26% of patients using SCr, respectively. Continuous UO-based alerts diagnosed stage ≥1 AKI 33.6 (IQR =15.43, 95.68) hours before stage ≥2 identified by SCr criteria. A SCr-based diagnosis of AKI stage ≥2 has been designated a Hospital Harm by the Centers for Medicare & Medicaid Services. Using this criterion as a benchmark, AKI alerts had a discriminative power of 0.78. The AKI Alert for stage 1 was significantly associated with increased intensive care unit and hospital length of stay and continuous renal replacement therapy, and stage ≥2 alerts were associated with mortality. CONCLUSIONS: AKI Alert, based on continuous UO and enabled by active drain line clearance, detected AKI stages 1 and 2 before SCr criteria. Early AKI detection allows for early kidney optimization, potentially improving patient outcomes.

Intra-abdominal hypertension in cardiac surgery patients: a multicenter observational sub-study of the Accuryn registry.

Intra-abdominal hypertension (IAH) is frequently present in the critically ill and is associated with increased morbidity and mortality. Conventionally, intermittent 'spot-check' manual measurements of bladder pressure in those perceived as high risk are used as surrogates for intra-abdominal pressure (IAP). True patterns of IAH remain unknown. We explored the incidence of IAH in cardiac surgery patients and describe the intra-and postoperative course of IAP using a novel, high frequency, automated bladder pressure measurement system. Sub-analysis of a prospective, multicenter, observational study (NCT04669548) conducted in three large academic medical centers. Continuous urinary output (CUO) and IAP measurements were observed using the Accuryn Monitoring System (Potrero Medical, Hayward, CA). Data collected included demographics, hemodynamic support, and high-frequency IAP and CUO. One Hundred Thirty-Seven cardiac surgery patients were analyzed intraoperatively and followed 48 h postoperatively in the intensive care unit. Median age was 66.4 [58.3, 72.0] years, and 61% were men. Median Foley catheter dwell time was 56.0 [46.8, 77.5] hours, and median baseline IAP was 6.3 [4.0, 8.1] mmHg. 93% (128/137) of patients were in IAH grade I, 82% (113/137) in grade II, 39% (53/137) in grade III, and 5% (7/137) in grade IV for at least 12 cumulative hours. For maximum consecutive duration of IAH, 84% (115/137) of patients spent at least 12 h in grade I, 62% (85/137) in grade II, 18% (25/137) in grade III, and 2% (3/137) in grade IV IAH. During the first 48 h after cardiac surgery, IAH is common and persistent. Improved and automated monitoring of IAP will increase the detection of IAH-which normally would remain undetected using traditional intermittent monitoring methods.

The impact of a postoperative multimodal analgesia pathway on opioid use and outcomes after cardiothoracic surgery.

OBJECTIVE: The Enhanced Recovery after Surgery Cardiac Society recommends using multimodal analgesia (MMA) for postoperative pain however, evidence-based guidelines have yet to be established. This study examines the impact of a standardized postoperative MMA pathway in reducing opioid consumption and related complications after cardiothoracic surgery (CTS). METHODS: Within a multicenter healthcare system, a postoperative MMA pathway was developed and implemented at two CTS intensive care units (ICU) while the other CTS ICU opted to maintain the existing opioid-based pathway. A retrospective chart review was conducted on patients admitted to a CTS ICU within this healthcare system after conventional coronary artery bypass grafting and/or valve surgery from September 1, 2018, to June 30, 2019. Comparative analysis was conducted on patients prescribed MMA versus those managed with an opioid-based pathway. The primary outcome was total opioid consumption, converted to morphine milligram equivalents, 72-h post-surgery. Secondary outcomes included mobility within one-day post-surgery, ICU length of stay (LOS), time to first bowel movement (BM), and time to first zero Richmond Agitation-Sedation Scale (RASS). RESULTS: Seven hundred sixty-two adults were included for final analysis. The MMA group had a higher body mass index, higher percentage of females, were more likely classified as African American and had higher scores for risk-adjusted complications. General Linear Model analysis revealed higher opioid consumption in the MMA group (Est. 0.22, p < 0.0009); however, this was not statistically significant after adjusting for differences in fentanyl usage. The MMA group was more likely to have mobility within one-day post-surgery (OR 0.44, p < 0.0001), have longer time to first BM (OR 1.93, p = 0.0011), and longer time to first zero RASS (OR 1.62, p = 0.0071). The analgesia groups were not a predictor for ICU LOS. CONCLUSIONS: Opioid consumption was not reduced secondary to this postoperative MMA pathway. The MMA group was more likely to have mobility within one-day post-surgery. Patients in the MMA group were also more likely to have prolonged time to first BM and first zero RASS. Development and evaluation of a perioperative MMA pathway should be considered.

Investigation of Water Interaction with Polymer Matrices by Near-Infrared (NIR) Spectroscopy.

The interaction of water with polymers is an intensively studied topic. Vibrational spectroscopy techniques, mid-infrared (MIR) and Raman, were often used to investigate the properties of water-polymer systems. On the other hand, relatively little attention has been given to the potential of using near-infrared (NIR) spectroscopy (12,500-4000 cm-1; 800-2500 nm) for exploring this problem. NIR spectroscopy delivers exclusive opportunities for the investigation of molecular structure and interactions. This technique derives information from overtones and combination bands, which provide unique insights into molecular interactions. It is also very well suited for the investigation of aqueous systems, as both the bands of water and the polymer can be reliably acquired in a range of concentrations in a more straightforward manner than it is possible with MIR spectroscopy. In this study, we applied NIR spectroscopy to investigate interactions of water with polymers of varying hydrophobicity: polytetrafluoroethylene (PTFE), polypropylene (PP), polystyrene (PS), polyvinylchloride (PVC), polyoxymethylene (POM), polyamide 6 (PA), lignin (Lig), chitin (Chi) and cellulose (Cell). Polymer-water mixtures in the concentration range of water between 1-10%(w/w) were investigated. Spectra analysis and interpretation were performed with the use of difference spectroscopy, Principal Component Analysis (PCA), Median Linkage Clustering (MLC), Partial Least Squares Regression (PLSR), Multivariate Curve Resolution Alternating Least Squares (MCR-ALS) and Two-Dimensional Correlation Spectroscopy (2D-COS). Additionally, from the obtained data, aquagrams were constructed and interpreted with aid of the conclusions drawn from the conventional approaches. We deepened insights into the problem of water bands obscuring compound-specific signals in the NIR spectrum, which is often a limiting factor in analytical applications. The study unveiled clearly visible trends in NIR spectra associated with the chemical nature of the polymer and its increasing hydrophilicity. We demonstrated that changes in the NIR spectrum of water are manifested even in the case of interaction with highly hydrophobic polymers (e.g., PTFE). Furthermore, the unveiled spectral patterns of water in the presence of different polymers were found to be dissimilar between the two major water bands in NIR spectrum (νs + νas and νas + δ).

Automated Intra-abdominal Pressure Monitoring During Orthotopic Heart Transplant Leads to Early Diagnosis and Treatment of Intraoperative Abdominal Compartment Syndrome-A Case Report.

We describe a case of spontaneous retroperitoneal hematoma leading to abdominal compartment syndrome and organ failure during a complicated orthotopic heart transplantation in a patient previously on mechanical circulatory support. After the patient had been weaned of cardiopulmonary bypass, the patient suddenly became hemodynamically unstable despite good LV and RV function. While the patient was resuscitated, high intra-abdominal pressures were noted on a novel monitor measuring real-time intra-abdominal pressures and urinary output. The early detection of high intra-abdominal pressures led to a swift decompressive laparotomy with the detection of retroperitoneal hematoma and subsequent hemodynamic stabilization.

Urinary catheter monitoring of intra-abdominal pressure after major abdominal surgery, a cost-benefit analysis.

OBJECTIVE: To estimate costs and benefits associated with measurement of intra-abdominal pressure (IAP). METHODS: We built a cost-benefit analysis from the hospital facility perspective and time horizon limited to hospitalization for patients undergoing major abdominal surgery for the intervention of urinary catheter monitoring of IAP. We used real-world data estimating the likelihood of intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and acute kidney injury (AKI) requiring renal replacement therapy (RRT). Costs included catheter costs (estimated $200), costs of additional intensive care unit (ICU) days from IAH and ACS, and costs of CRRT. We took the preventability of IAH/ACS given early detection from a trial of non-surgical interventions in IAH. We evaluated uncertainty through probabilistic sensitivity analysis and the effect of individual model parameters on the primary outcome of cost savings through one-way sensitivity analysis. RESULTS: In the base case, urinary catheter monitoring of IAP in the perioperative period of major abdominal surgery had 81% fewer cases of IAH of any grade, 64% fewer cases of AKI, and 96% fewer cases of ACS. Patients had 1.5 fewer ICU days attributable to IAH (intervention 1.6 days vs. control of 3.1 days) and a total average cost reduction of $10,468 (intervention $10,809, controls $21,277). In Monte Carlo simulation, 86% of 1,000 replications were cost-saving, for a mean cost savings of $10,349 (95% UCI $8,978, $11,720) attributable to real-time urinary catheter monitoring of intra-abdominal pressure. One-way factor analysis showed the pre-test probability of IAH had the largest effect on cost savings and the intervention was cost-neutral at a prevention rate as low as 2%. CONCLUSIONS: In a cost-benefit model using real-world data, the potential average in-hospital cost savings for urinary catheter monitoring of IAP for early detection and prevention of IAH, ACS, and AKI far exceed the cost of the catheter.

A Screening Tool to Detect Chronic Critically Ill Cardiac Surgery Patients at Risk for Low Levels of Testosterone and Somatomedin C: A Prospective Observational Pilot Study.

Objective The neuroendocrine response to critical illness is dichotomous as it is adaptive during the acute phase then transitions to maladaptive as critical illness becomes prolonged in 25-30% of patients. Presently, monitoring all critically ill patients for endocrinopathies is not the standard of care. However, given the negative impact on patient prognosis, a need to identify those at risk for endocrinopathies, may exist. Thus, a screening tool to identify endocrinopathies along the somatotroph and gonadal axes in a cardiothoracic surgery population was developed. Methods A prospective observational pilot study was conducted in two cardiothoracic surgery intensive care units (ICU) within a multi-site healthcare system. Total testosterone and somatomedin C levels were obtained from 20 adult patients who remained in the ICU for greater than seven days after cardiothoracic surgery and were tolerating nutrition, had a risk of malnutrition and a mobility score of moderate to dependent assistance. Results Twenty patients were included for descriptive analysis (seven females). Thirteen patients tested low for total testosterone, with males more likely to have a testosterone-related endocrinopathy as compared to females (100% vs. 0 to 43%, p = 0.0072). A higher proportion of low somatomedin C levels was found in females than males (57% vs. 31%); however, the difference was not statistically significant (p = 0.251). Conclusions The screening tool used in this pilot study accurately predicted low total testosterone in all men and reasonably predicted low somatomedin C in a majority of women. However, the ability of the tool to predict low total testosterone in women and low somatomedin C in men is less certain. A gender-specific screening tool might be necessary to predict hormonal deficiencies.

Erector Spinae Regional Anesthesia for Robotic Coronary Artery Bypass Surgery Is Not Associated With Reduced Postoperative Opioid Use: A Retrospective Observational Study.

OBJECTIVE: Regional anesthesia techniques are gaining traction in cardiac surgery. The aim of this study was to compare the analgesic efficacy of erector spinae plane block catheters (ESPBC), serratus anterior plane block catheters (SAPBC), and paravertebral single-shot block (PVB) versus no block after robotic minimally invasive direct coronary artery bypass (MIDCAB). DESIGN: This was a retrospective observational study of routinely recorded data. SETTING: The study was performed at a single healthcare system. PARTICIPANTS: All patients underwent robotic MIDCAB. INTERVENTION: Data were analyzed from 346 patients during a 53-month period. The clinical data warehouse was queried for all robotic MIDCAB surgeries. Variables abstracted included type of nerve block, age, sex, use of adjuncts, Society of Thoracic Surgeons predicted short length of stay (PSLOS), total opioid consumption during the 72 hours after surgery, and postoperative hospital length of stay (LOS). The primary outcome was total oral morphine milligram equivalents (MME) consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS. MEASUREMENTS AND MAIN RESULTS: In a model adjusting for PSLOS, the authors did not observe an association between ESPBC and the reduction of total administered oral MME within 72 hours after surgery. There was no significant difference in MME when comparing patients who received PVB to patients with ESPBC. Older age and female sex were associated with significantly lower MME. Patients who received ESPBC had a significantly shorter hospital LOS than patients with SAPBC. CONCLUSIONS: These findings suggested that postoperative pain after MIDCAB surgery might not be completely covered by ESPBC. Prospective studies are needed to further elucidate the value of this technique for robotic MIDCAB.

Impact of COVID-19 response on global surgical volumes: an ongoing observational study.

OBJECTIVE: To determine whether location-linked anaesthesiology calculator mobile application (app) data can serve as a qualitative proxy for global surgical case volumes and therefore monitor the impact of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We collected data provided by users of the mobile app "Anesthesiologist" during 1 October 2018-30 June 2020. We analysed these using RStudio and generated 7-day moving-average app use plots. We calculated country-level reductions in app use as a percentage of baseline. We obtained data on COVID-19 case counts from the European Centre for Disease Prevention and Control. We plotted changing app use and COVID-19 case counts for several countries and regions. FINDINGS: A total of 100 099 app users within 214 countries and territories provided data. We observed that app use was reduced during holidays, weekends and at night, correlating with expected fluctuations in surgical volume. We observed that the onset of the pandemic prompted substantial reductions in app use. We noted strong cross-correlation between COVID-19 case count and reductions in app use in low- and middle-income countries, but not in high-income countries. Of the 112 countries and territories with non-zero app use during baseline and during the pandemic, we calculated a median reduction in app use to 73.6% of baseline. CONCLUSION: App data provide a proxy for surgical case volumes, and can therefore be used as a real-time monitor of the impact of COVID-19 on surgical capacity. We have created a dashboard for ongoing visualization of these data, allowing policy-makers to direct resources to areas of greatest need.

Regional anesthesia considerations for cardiac surgery.

Pain is a significant consequence of cardiac surgery and newer techniques in cardiac anesthesia have provided an impetus for the development of multimodal techniques to manage acute pain in this setting. In this regard, regional anesthesia techniques have been increasingly used in many cardiac surgical procedures, for the purposes of reducing perioperative consumption of opioid agents and enhanced recovery after surgery. The present investigation focuses on most currently used regional techniques in cardiac surgical procedures. These regional techniques include chest wall blocks (e.g., PECS I and II, SAP, ESB, PVB), sternal blocks (e.g., TTMPB, PSINB), and neuraxial blocks (e.g., TEA, high spinal anesthesia). The present investigation also summarizes indications, technique, complications, and potential clinical benefits of these evolving regional techniques. Cardiac surgery patients may benefit from application of these regional techniques with well controlled indications and careful patient selections.

A Case of Multifactorial Diabetic Ketoacidosis Acquired in the Intensive Care Unit: A Case Report.

Diabetic ketoacidosis (DKA) is a potentially fatal endocrine emergency resulting from uncontrolled diabetes mellitus (DM). The development of DKA has been linked to a number of precipitating factors such as infectious process, ischemia, medications, and other medical-surgical illnesses. These factors have been found to aggravate or unmask pre-existing glucose dysregulation secondary to absolute or relative insulin deficiency and increased levels of counter-regulatory hormones. We describe the case of a 61-year-old male with a history of insulin dependent DM who develops DKA postoperatively after a three-vessel coronary artery bypass surgery and mitral valve repair while in the intensive care unit (ICU). The patient's postoperative course was complicated by presumed pneumonia and hyperactive delirium. On postoperative day (POD) five, the patient's insulin infusion was held due to non-symptomatic hypoglycemia. Eleven hours later, the insulin infusion was resumed to treat DKA after laboratory findings revealed hyperglycemia, an elevated ß-hydroxybutyrate, and anion gap metabolic acidosis. Multiple contributing factors for the development of DKA are suspected and discussed. It is paramount that clinicians are knowledgeable of the multiple factors that can contribute to the development of DKA in the ICU.

Association of Serratus Anterior Plane Block for Minimally Invasive Direct Coronary Artery Bypass Surgery With Higher Opioid Consumption: A Retrospective Observational Study.

OBJECTIVE: The optimal regional technique for minimally invasive direct coronary artery bypass (MIDCAB) has yet to be determined. The aim of this study was to compare the efficacy of ultrasound-guided serratus anterior plane block (SAPB) with paravertebral block (PVB) and no block for controlling acute thoracotomy pain after robotic-assisted coronary artery bypass grafting (CABG). DESIGN: This is a retrospective study. Multiple variable regression analyses were performed. SETTING: The study was performed as a single institution. PARTICIPANTS: All patients underwent robotic-assisted CABG. INTERVENTION: Data were analyzed from 197 patients during a 27-month period. Charts were abstracted manually to ascertain type of nerve block, age, gender, use of home opioids, use of adjuncts for opioid reduction, Society of Thoracic Surgeons predicted long length of stay (LOS), total opioid consumption during the 72 hours after surgery, and postoperative LOS. The authors' primary outcome was total morphine equivalents consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS. MEASUREMENTS AND MAIN RESULTS: Patients who received SAPB did not have significantly different opioid consumption than patients who had no block (p = 0.15), but it was increased significantly compared to patients administered PVB (PVB v SAPB catheter, p = 0.049; PVB v SAPB single shot, p = 0.049). There were no significant differences between groups in terms of postoperative LOS. CONCLUSION: These findings suggest SAPB might not cover adequately the incisional and tube pain associated with MIDCAB. If validated by prospective studies, these findings suggest that SAPB should be considered only for patients who are not candidates for PVB.

Successful Management of a Patient With Possible Mast Cell Activation Syndrome Undergoing Pulmonary Embolectomy: A Case Report.

We report the successful perioperative management of a patient with presumed mastocytosis undergoing pulmonary embolectomy. Postoperatively the patient went into vasodilatory shock, which was partly attributed to mast cell mediator release. H1- and H2-antagonists, steroids, and a single dose of methylene blue were given with improvement of hemodynamics. The patient was weaned off vasoactive substances and extubated by postoperative day 2. We discuss the perioperative management of patients with mastocytosis, briefly review the literature concerning anesthetic management for cardiac surgery in patients with this disorder, and discuss our patient's alternative but related diagnosis of idiopathic mast cell activation syndrome.

Antipsychotic-Induced Neuroleptic Malignant Syndrome After Cardiac Surgery.

We report a case of neuroleptic malignant syndrome (NMS) in a postoperative cardiac surgery patient after the administration of typical and atypical antipsychotics for the treatment of delirium. On postoperative day 8, the patient's temperature peaked at 40.6°C. Agitation, rigidity, elevation in creatine kinase, and leukocytosis were associated findings. NMS was suspected on postoperative day 10. All antipsychotics were discontinued; dantrolene infusions and fluid therapy were initiated. After 2 days of NMS treatment, the patient's symptoms resolved. The temporal relationship between discontinuation of all antipsychotics, initiation of dantrolene, and clinical improvement supports the diagnosis of antipsychotic-induced NMS.

Pharmacokinetics of single-dose intravenous ketorolac in infants aged 2-11 months.

BACKGROUND: Ketorolac is a parenterally available nonsteroidal antiinflammatory drug that nonselectively inhibits cyclooxygenase. Ketorolac is an attractive alternative to opioids in the pediatric population because of its favorable side effect profile; it provides postoperative analgesia similar to morphine, but is associated with significantly less respiratory depression, pruritus, and emesis. Despite the efficacy of ketorolac in young patients, there are minimal data to characterize the pharmacokinetic variables of ketorolac in infants younger than 6 months. METHODS: In this study, 17 infants younger than 1 year old, without renal or liver disease, undergoing elective surgery received a single-dose of IV ketorolac 0.5 mg/kg. Blood was sampled at 0, 5, 10, 15, 30, 60, and 120 minutes, and at 4, 6, 12, and 24 hours. Ketorolac levels were analyzed using a specific and validated high-performance liquid chromatography method with mass spectrometry (LC-LC/MS/MS). Pharmacokinetic analysis of individual subjects and population pharmacokinetic modeling was performed using SAAM II and PopKinetics, respectively (SAAM Institute, University of Washington). RESULTS: Characterization of pharmacokinetic parameters was possible in 14 subjects. The data were best described by a 2-compartment model. Estimated individual parameters were clearance 1.49 ± 1.12 mL/min/kg, Vss (volume of distribution at steady state) 0.31 ± 0.11 L/kg, and half-life of 236 ± 169 minutes. Estimated population pharmacokinetic parameters were clearance 1.52 mL/min/kg and Vss 0.29 L/kg. There was a trend toward lower clearances in younger patients. CONCLUSION: This is the first report of individualized pharmacokinetic parameters of ketorolac in children in which the majority of subjects were younger than 6 months old.

Effects of lovastatin on breast cancer cells: a proteo-metabonomic study.

INTRODUCTION: Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation and reduction of signals driving cell proliferation and survival responses. METHODS: In this study we evaluated the effects of lovastatin acid and lactone on breast cancer MDAMB231 and MDAMB468 cells using a combination of proteomic and metabonomic profiling techniques. RESULTS: Lovastatin inhibited proliferation of breast cancer cell lines. MDAMB231 cells were more sensitive to its effects, and in most cases lovastatin acid showed more potency towards the manipulation of protein expression than lovastatin lactone. Increased expression of Rho inhibitor GDI-2 stabilized the non-active Ras homolog gene family member A (RhoA) leading to a decreased expression of its active, membrane-bound form. Its downstream targets cofilin, CDC42 and G3BP1 are members of the GTPase family affected by lovastatin. Our data indicated that lovastatin modulated the E2F1-pathway through the regulation of expression of prohibitin and retinoblastoma (Rb). This subsequently leads to changes of E2F-downstream targets minichromosome maintenance protein 7 (MCM7) and MutS homolog 2 (MSH2). Lovastatin also regulated the AKT-signaling pathway. Increased phosphatase and tensin homolog (PTEN) and decreased DJ-1 expression lead to a down-regulation of the active pAkt. Lovastatin's involvement in the AKT-signaling pathway was confirmed by an upregulation of its downstream target, tumor progressor NDRG1. Metabolic consequences to lovastatin exposure included suppression of glycolytic and Krebs cycle activity, and lipid biosynthesis. CONCLUSIONS: The combination of proteomics and metabonomics enabled us to identify several key targets essential to the antitumor activity of lovastatin. Our results imply that lovastatin has the potential to reduce the growth of breast cancer cells.