A risk stratification algorithm using non-invasive respiratory volume monitoring to improve safety when using post-operative opioids in the PACU.

Late detection of respiratory depression in non-intubated patients compromises patient safety. SpO2 is a lagging indicator of respiratory depression and EtCO2 has proven to be unreliable in non-intubated patients. A decline in minute ventilation (MV) is the earliest sign of respiratory depression. A non-invasive respiratory volume monitor (RVM) that provides accurate, continuous MV measurements enables clinicians to predict and quantify respiratory compromise. For this observational study, practitioners were blinded to the RVM measurements and pain management followed the usual routine. Patients were stratified by their MV on PACU admission and classified as "At-Risk" or "Not-At-Risk," with progression to "Low MV" status following opioids assessed for each category. The purpose was to determine if stratifying based on MV on PACU arrival could identify patients at higher risk for respiratory depression. Ability to identify in advance patients at higher risk for respiratory depression following standard opioid dosing would drive changes in pain management and improve patient care. RVM and opioid administration data from 150 PACU patients following elective joint-replacement surgery were collected in an observational study. "Predicted" MV (MVPRED) and "Percent Predicted" (MVMEASURED/MVPRED × 100 %) were calculated for each patient using standard formulas. Prior to opioid administration, patients were classified as either "Not-At-Risk" (MV ≥ 80 % MVPRED) or "At-Risk" (MV < 80 % MVPRED). "Low MV" was defined as MV < 40 % MVPRED. Post-operative apnea (POA) was defined as ≥5 ten-second apneas per hour of PACU stay. We compared the incidences of Low MV following a single opioid dose, POA, and Low MV at discharge for both groups. In the PACU, 74/150 patients received opioids. Within 15 min of opioid administration, 32 % (24/74) developed Low MV. The risk-stratification algorithm identified 22/24 patients (92 % sensitivity). Only 46 % of them had POA, and the majority had Low MV without POA. At discharge, 29/150 patients had Low MV and those receiving opioids were 50 % more likely to display Low MV (23 vs. 16 %). The RVM can identify patients at-risk for opioid-induced respiratory depression and/or experiencing POA. Monitoring of MV can guide opioid-dosing regimens and may increase patient safety across the continuum of care.

Non-invasive respiratory volume monitoring identifies opioid-induced respiratory depression in an orthopedic surgery patient with diagnosed obstructive sleep apnea: a case report.

INTRODUCTION: Obstructive sleep apnea and opioid-induced respiratory depression can unpredictably threaten respiratory competence in the post-anesthesia care unit. Current respiratory monitoring relies heavily on respiratory rate and oxygen saturation, as well as subjective clinical assessment. These assessments have distinct limitations, and none provide a real-time, objective, quantitative direct measurement of respiratory status. A novel, non-invasive respiratory volume monitor uses bioimpedance to provide accurate, quantitative measurements of minute ventilation, tidal volume and respiratory rate continuously in real time, providing a direct measurement of ventilation. CASE PRESENTATION: The case describes an orthopedic surgery patient (54-year-old Caucasian man, body mass index 33.7 kg/m(2)) with diagnosed obstructive sleep apnea in whom the respiratory volume monitor data depicted persistent apneic behavior undetected by other monitoring. The monitor was able to detect a sudden reduction in minute ventilation after initial opioid administration in the post-anesthesia care unit. The patient had sustained low minute ventilation until discharge. Neither respiratory rate data from the hospital monitor nor oxygen saturation readings reflected the respiratory decompensation, remaining within normal limits even during sustained low minute ventilation. CONCLUSIONS: The events of this case illustrate the limitations of current respiratory rate monitoring and pulse oximetry in the evaluation of post-surgical respiratory status. Our patient displayed stable respiratory rate and no evidence of desaturation, despite sustained low minute ventilation, and he received opioids in the post-anesthesia care unit despite already compromised ventilation. Because the available monitoring did not indicate the patient's true respiratory status, he was treated with additional opioids, markedly increasing his risk for further respiratory decline.

The evaluation of a non-invasive respiratory volume monitor in surgical patients undergoing elective surgery with general anesthesia.

Continuous respiratory assessment is especially important during post-operative care following extubation. Respiratory depression and subsequent adverse outcomes can arise due to opioid administration and/or residual anesthetics. A non-invasive respiratory volume monitor (RVM) has been developed that provides continuous, real-time, measurements of minute ventilation (MV), tidal volume (TV), and respiratory rate (RR) via a standardized set of thoracic electrodes. Previous work demonstrated accuracy of the RVM versus standard spirometry and its utility in demonstrating response to opioids in postoperative patients. This study evaluated the correlation between RVM measurements of MV, TV and RR to ventilator measurements during general anesthesia (GA). Continuous digital RVM and ventilator traces, as well as RVM measurements of MV, TV and RR, were analyzed from ten patients (mean 62.6±7.4 years; body mass index 28.6±5.2 kg/m2) undergoing surgery with GA. RVM data were compared to ventilator data and bias, precision and accuracy were calculated. The average MV difference between the RVM and ventilator was -0.10 L/min (bias: -1.3%, precision: 6.6%, accuracy: 9.0%. The average TV difference was 40 mL (bias: 0.4%, precision: 7.3%, accuracy: 9.1%). The average RR difference was -0.22 breaths/minute (bias: -1.8%, precision: 3.7% accuracy: 4.1%). Correlations between the RVM traces and the ventilator were compared at various points with correlations>0.90 throughout. Pairing the close correlation to ventilator measurements in intubated patients demonstrated by this study with previously described accuracy compared to spirometry in non-intubated patients, the RVM can be considered to have the capability to provide continuity of ventilation monitoring post-extubation This supports the use of real-time continuous RVM measurements to drive post-operative and post-extubation protocols, initiate therapeutic interventions and improve patient safety.

Continuous noninvasive respiratory volume monitoring for the identification of patients at risk for opioid-induced respiratory depression and obstructive breathing patterns.

BACKGROUND: Opioid-induced respiratory depression (OIRD) and postoperative apnea (POA) can lead to complications after surgery or traumatic injury. Previously, real-time monitoring of respiratory insufficiency and identification of apneic events have been difficult. A noninvasive respiratory volume monitor (RVM) that reports minute ventilation (MV), tidal volume, and respiratory rate is now available. The RVM was used to report the effect of opioids on respiratory status as well as demonstrate apneic breathing patterns in a hospital postanesthesia care unit. METHODS: RVM traces were collected from 132 patients. Predicted MV (MVPRED) for each patient was used to calculate and the "percent predicted" MV (MVMEASURED / MVPRED × 100%) before opioid administration. Patients were stratified patients into two categories: "at risk," MV of less than 80% MVPRED, and "not at risk," MV of 80% MVPRED or greater. After opioid dosing, patients with MV of less than 40% MVPRED were categorized as "unsafe." POA was defined as more than five apneic or hypopneic events per hour. RESULTS: Of the 132 patients, 50 received opioids. Baseline MV was 7.2 ± 0.5 L/min. The MV-based protocol classified 18 of 50 patients as at risk before opioid administration. After the first opioid dose administration, at-risk patients experienced an average MV decrease (36.7% ± 8.5% MVPRED) and 13 of 18 decreased into unsafe; the 32 not at-risk patients experienced a lesser average MV decrease (76.9% ± 6.3% MVPRED). Only 1 of 32 not at-risk patients had a decrease in MV to unsafe. The proposed protocol had a sensitivity of 93% and a specificity of 86%. Of the 132 patients, 26 displayed POA. Of the 26 patients, 12 experienced POA without receiving opioids. Of the 26 patients with POA, 14 also received opioids, and of those, 6 were classified as unsafe. CONCLUSION: This investigation indicates that at risk and unsafe respiratory patterns occur frequently after procedure. RVM provides continuous noninvasive objective measurements of OIRD and POA. The RVM may prove a useful tool in opioid dosing and in recognition and management of POA and strong potential value in the rapid detection of OIRD and apnea in the contemporary combat casualty environment. LEVEL OF EVIDENCE: Care management study, level V.

Non-invasive respiratory volume monitoring to detect apnea in post-operative patients: case series.

Obstructive sleep apnea (OSA) is a potential independent risk factor for postoperative complications, adverse surgical outcomes, and longer hospital stays. Obese patients with OSA have increased post-operative complications. An estimated 25-30% of pre-operative patients are at a high risk for OSA. A novel, non-invasive respiratory volume monitor (RVM) has been developed to provide a real time respiratory curve demonstrating lung volumes as well as a continuous, display of minute ventilation, tidal volume and respiratory rate. Clinical application of this device in the post-anesthesia care unit (PACU) can "unmask" post-operative apneic events resulting from partial or complete airway collapse due to the residual effects of narcotic administration and volatile and/or intravenous anesthetics. Clinical examples from two patients, one with known OSA and one without a previous diagnosis of OSA, monitored in the PACU with RVM are presented here. Post-operatively both patients had an increase in apneic episodes with significant decreases in their MV during apneic episodes after opioid administration as compared to pre-op baseline. In addition, oxygen saturation, for both patients, which is an essential component of current respiratory monitoring remained normal in the cases presented, despite the significant decreases in MV. Continuous RVM monitoring demonstrates both changes in respiratory patterns and overall adequacy of ventilation, and allows practitioners to quantify the increase in the number and duration apneic episodes as a response to narcotic administration. These case studies demonstrate that a non-invasive respiratory volume monitoring system can detect and quantify respiratory disturbances that currently go undetected.

Special article: evaluation of a novel noninvasive respiration monitor providing continuous measurement of minute ventilation in ambulatory subjects in a variety of clinical scenarios.

BACKGROUND: Currently there is no technology that noninvasively measures the adequacy of ventilation in nonintubated patients. A novel, noninvasive Respiratory Volume Monitor (RVM) has been developed to continuously measure and display minute ventilation (MV), tidal volume (TV), and respiratory rate (RR) in a variety of clinical settings. We demonstrate the RVM's accuracy and precision as compared with a standard spirometer under a variety of clinically relevant breathing patterns in nonintubated subjects. METHODS: Thirty-one voluntary subjects completed the primary study. MV, TV, and RR measurements were collected from the RVM and spirometer simultaneously for each participant on day 1 and day 2 and analyzed to determine accuracy, precision, and bias for normal, fast, slow, irregular, and closed-glottis breathing. RESULTS: Data demonstrated that RVM and spirometer measurements of MV and TV are equivalent in a wide range of ambulatory subjects with an average error <10% (95% confidence interval for accuracy <16%, precision <12%, and bias <11%). Repeated measures analysis of variance found no significant difference between spirometry and RVM individual measurements of MV, TV, and RR (P > 0.7), whereas a paired-difference equivalent test demonstrated, with 99% power, that both MV and TV measurements from the 2 devices are equivalent within ±15%. CONCLUSIONS: This study demonstrates RVM's clinically relevant accuracy and precision in measuring MV, TV, and RR over a 24-hour period and during various breathing patterns.

The ultrasound-guided retrolaminar block.

PURPOSE: Paravertebral blocks have gained in popularity and offer the possible benefit of reduced adverse effects when compared with epidural analgesia. Nevertheless, pulmonary complications in the form of inadvertent pleural puncture are still a recognized risk. Also, the traditional paravertebral blocks are often technically difficult even with ultrasound guidance and constitute deep non-compressible area injections. We present our experience with the first three patients receiving ultrasound-guided retrolaminar blocks for managing the pain associated with multiple rib fractures. CLINICAL FEATURES: The vertebral laminae are identified by ultrasound imaging in a paramedian sagittal plane by sequentially visualizing the pleura and ribs, transverse processes, and the corresponding laminae (from lateral to medial). The block needle is guided to contact the lamina, and the local anesthetic injectate is visualized under real-time imaging. A catheter is inserted and used for continuous analgesia. In three consecutive patients, verbal rating scale (VRS) pain scores were reduced from 10/10 to less than 5/10, and no technical difficulties, complications, or adverse effects were encountered. CONCLUSIONS: Successful analgesia was achieved in all three cases utilizing continuous infusion and intermittent boluses with ultrasound-guided retrolaminar blocks. These results show the feasibility of this approach for patients with multiple rib fractures.

A comparison of the speed, success rate, and retention of rescue airway devices placed by first-responder emergency medical technicians: a high-fidelity human patient simulation study.

BACKGROUND: Current airway management for most first-responder basic emergency medical technicians (EMT-Bs) does not include the use of blind-advanced-airway devices. OBJECTIVE: To compare the speed, success rates, and skill retention with which EMT-Bs providers can place three blind-advanced-airway devices. METHODS: Prospective study of 43 EMT-Bs trained in the use of the Esophageal-Tracheal-Combitube(®) (ETC), King LT(®) (KLT), and Laryngeal Mask Airway(™) (LMA). The time it took each participant to place each device correctly and ventilate a human patient simulator was assessed. Primary outcome measures were the success rate of proper insertion for each device and time interval from initiation of mouth insertion to initiation of chest rise. To assess skill retention, at 3 months the providers were reassessed under exact conditions. RESULTS: At Day 1, time required to place an ETC, LMA, and KLT were 32.7 ± 12.3, 19.2 ± 6.2, and 20.1 ± 6.6 s, respectively. Using paired t-tests, LMA and KLT were faster than ETC, p < 0.0001. At 3 months, pair-wise comparisons showed the ETC took longer to place than the KLT and LMA, p < 0.0001; and the LMA took longer to place than the KLT, p = 0.0034 (36.4 ± 13.1 ETC, 24.8 ± 12.4 LMA, 19.0 ± 6.9 KLT). There was no statistical difference of failures in placing any device. CONCLUSIONS: Comparison of three rescue airway devices placed by EMT-Bs providers showed that it takes significantly longer to place an ETC compared to an LMA and KLT both on Day 1 and 3 months later. Three-month retention studies revealed that it took significantly longer to place an LMA compared to the KLT.

Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer.

Human S100A7 (psoriasin) is considered a marker for specific stages of breast cancer. hS100A15 is almost identical to hS100A7 and difficult to discriminate. We developed specific probes to distinguish hS100A7 and hS100A15, and demonstrate their differential distribution in normal breast tissue. Further, hS100A7 and S100A15 transcripts are elevated in ER/PR negative breast cancers, but hS100A15 protein is detected in all cancer specimens while hS100A7 protein is sporadically expressed. The differential regulation, expression and distribution of hS100A7 and hS100A15 and their reported distinct functions are compelling reasons to discriminate among these proteins in normal breast and breast cancers.

Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.

Human S100A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation.

Purification, crystallization and preliminary X-ray diffraction of human S100A15.

Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2 kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8 angstroms, alpha = 71.2, beta = 68.1, gamma = 67.8 degrees and an estimated two molecules in the asymmetric unit, and diffract to 1.7 angstroms resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2 angstroms, beta = 128.2 degrees and an estimated one molecule in the asymmetric unit, and diffract to 2.0 angstroms resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7.

The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation.

The calcium-binding proteins of the human S100A7/A15 (hS100A7/A15) subfamily are differentially expressed in normal and pathological epidermis. The hS100A7 (psoriasin) and S100A15 reside in a chromosomal cluster of highly similar paralogs. To exploit the power of mouse models for determining functions of gene products, the corresponding S100A7/A15 ortholog was cloned and examined in murine skin. The single mouse S100A15 (mS100A15) gene encodes a protein of 104 amino acids with a predicted molecular weight of 12,870 Da and two EF-hand calcium binding sites. Using gene-specific primers and specific antibodies, expression of mS100A15 in both skin and isolated keratinocytes is confined to differentiating granular and cornified epidermal cells. Immunoblotting of epidermal extracts revealed a series of high molecular weight bands that are also recognized by an antibody for transglutaminase-mediated protein crosslinks. mS100A15 expression is upregulated in cultured keratinocytes induced to differentiate by calcium or phorbol esters. Maximal induction occurs concordantly with expression of late differentiation markers. Induction is enhanced in keratinocytes overexpressing protein kinase Calpha and is dependent on activator protein-1 transcription factors. The regulation, expression pattern and crosslinking of mS100A15 are consistent with the characteristics of the human orthologs, providing a valid surrogate model to study changes in these proteins associated with cutaneous pathologies.