Resting Physiologic Dead Space as Predictor of Postoperative Pulmonary Complications After Robotic-Assisted Lung Resection: A Pilot Study.

Lung resection surgery carries significant risks of postoperative pulmonary complications (PPC). Cardiopulmonary exercise testing (CPET) is performed to predict risk of PPC in patients with severely reduced predicted postoperative forced expiratory volume in one second (FEV1) and diffusion of carbon monoxide (DLCO). Recently, resting end-tidal partial pressure of carbon dioxide (PETCO2) has been shown as a good predictor for increased risk of PPC. However, breath-breath breathing pattern significantly affects PETCO2. Resting physiologic dead space (VD), and physiologic dead space to tidal volume ratio (VD/VT), may be a better predictor of PPC than PETCO2. The objective of this study was to prospectively determine the utility of resting measurements of VD and VD/VT in predicting PPC in patients who underwent robotic-assisted lung resection for suspected or biopsy-proven lung malignancy. Thirty-five consecutive patients were included in the study. Patients underwent preoperative pulmonary function testing, symptom-limited CPET, and a 6-min walk test. In the first 2 min prior to the exercise portion of the CPET, we obtained resting VT, minute ventilation ( V ˙ E), VD (less instrument dead space), VD/VT, PETCO2, and arterial blood gases. PPC within 90 days were recorded. Fourteen (40%) patients had one or more PPC. Patients with PPC had significantly elevated resting VD compared to those without (0.318 ± 0.028 L vs. 0.230 ± 0.017 L (± SE), p < 0.006), and a trend toward increased VD/VT (0.35 ± 0.02 vs. 0.31 ± 0.02, p = 0.051). Area under the receiver operating characteristic (ROC) for VD was 0.81 (p < 0.002), VD/VT was 0.68 (p = 0.077), and PETCO2 was 0.52 (p = 0.840). Peak V ˙ O2, V ˙ E/ V ˙ CO2 slope, pulmonary function tests, 6-min walk distance and arterial blood gases were similar between the two groups. Intensive care unit and total hospital length of stay was significantly longer in those with PPC. In conclusion, preoperative resting VD was significantly elevated in patients with PPC. The observed increase in resting VD may be a potentially useful predictor of PPC in patients undergoing robotic-assisted lung resection surgery for suspected or biopsy-proven lung malignancy. A large prospective study is needed for confirmation.

Noninvasive ventilation: education and training. A narrative analysis and an international consensus document.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries.

Teflon Injection into the Trachea Causes Predictable Fibroblastic Response and Collagen Deposition: A Pilot Study.

BACKGROUND: Expiratory central airway collapse is an increasingly recognized abnormality of the central airways and may be present in as many as 22% of patients evaluated for chronic obstructive pulmonary disease and/or asthma. Many current treatment options require invasive procedures that have been shown to cause significant morbidity and mortality. To test the hypothesis that Teflon injection will induce sufficient fibroblast proliferation and collagen deposition, we evaluated the time course on the effect of Teflon injection in the posterior membranous trachea on the histopathology of the tracheobronchial tree. METHODS: Six Yucatan Pigs were assigned to undergo general anesthesia and injection of 0.3 to 0.5 mL of sterile Teflon paste in 50% glycerin into the posterior membranous tracheal wall. A control pig received an equivalent volume of glycerin. Animals were euthanized in predefined intervals and tracheas were excised and examined under light microscopy for identifying fibroblast proliferation and collagen deposition. RESULTS: Compared with the control pig, the Teflon injection site showed tissue reaction of fibrohistiocytic proliferation and subsequent collagen deposition in all animals. Furthermore, the increased fibroblast proliferation and collagen deposition were time dependent (P<0.01). CONCLUSION: This pilot study demonstrates histopathologic changes in the trachea after Teflon injection, comprised of increased fibroblast activity and collagen deposition that could be of potential use in creating greater airway rigidity in patients with sever diffuse excessive dynamic airway collapse.

Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis.

OBJECTIVES: Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 and thiamin transporter-2), and mitochondrial thiamin pyrophosphate transporter. DESIGN: Randomized controlled study. SETTING: Research laboratory at a Veterans Affairs Medical Center. SUBJECTS: Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate, and severe sepsis with equal number of animals in each group. INTERVENTIONS: Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25%, 50%, and 75% of cecal length, defined as severe, moderate, and mild sepsis, respectively. Control animals underwent laparotomy only. MEASUREMENTS AND MAIN RESULTS: After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [H]thiamin. Expressions of thiamin transporter-1, thiamin transporter-2, and mitochondrial thiamin pyrophosphate transporter proteins and messenger RNA were measured. Proinflammatory cytokines (interleukin-1ß and interleukin-6) and adenosine triphosphate were also measured. Sepsis inhibited [H]thiamin uptake, and the inhibition was a function of sepsis severity. Both cell membrane thiamin transporters and mitochondrial thiamin pyrophosphate transporter expression levels were suppressed; also levels of adenosine triphosphate in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham-operated controls. CONCLUSIONS: For the first time, we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and mitochondrial thiamin pyrophosphate transporter, leading to adenosine triphosphate depletion.

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits.

INTRODUCTION: Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties. METHODS: The PEEP level (8 cmH2O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA. RESULTS: PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated. CONCLUSIONS: Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.

Successful closure of bronchopleural fistula with Xeroform dressing.

Bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree, and is associated with significant morbidity and mortality. Treatment options for BPF include surgical closure and medical therapy. In an unstable patient, invasive surgical intervention is not an option. In this article, we report the case of a 61-year-old man who developed pneumothorax with a large BPF after a bronchoscopic resection of a malignant endobronchial lesion. We inserted a piece of 1.5×1.5-cm Xeroform dressing to seal the massive air leak with successful closure of the BPF. To our knowledge, this is the first report of successful closure of a massive BPF with Xeroform dressing in an acutely decompensating patient.

Interactive effects of corticosteroid and mechanical ventilation on diaphragm muscle function.

Information on the interactive effects of methylprednisolone, controlled mechanical ventilation (CMV), and assisted mechanical ventilation (AMV) on diaphragm function is sparse. Sedated rabbits received 2 days of CMV, AMV, and spontaneous breathing (SB), with either methylprednisolone (MP; 60 mg/kg/day intravenously) or saline. There was also a control group. In vitro diaphragm force, myofibril ultrastructure, αII-spectrin proteins, insulin-like growth factor-1 (IGF-1), and muscle atrophy F-box (MAF-box) mRNA were measured. Maximal tetanic tension (P(o)) decreased significantly with CMV. Combined MP plus CMV did not decrease P(o) further. With AMV, P(o) was similar to SB and controls. Combined MP plus AMV or MP plus SB decreased P(o) substantially. Combined MP plus CMV, MP plus AMV, or MP plus SB induced myofibrillar disruption that correlated with the reduced P(o). αII-spectrin increased, IGF-1 decreased, and MAF-box mRNA increased in both the CMV group and MP plus CMV group. Short-term, high-dose MP had no additive effects on CMV-induced diaphragm dysfunction. Combined MP plus AMV impaired diaphragm function, but AMV alone did not. We found that acute, high-dose MP produces diaphragm dysfunction depending on the mode of mechanical ventilation.

Acute effects of high-dose methylprednisolone on diaphragm muscle function.

The time- and dose-dependent effects of acute high-dose corticosteroids on the diaphragm muscle are poorly defined. This study aimed to examine in rabbits the temporal relationships and dose-response effects of acute high-dose methylprednisolone succinate on diaphragmatic contractile and structural properties. Animals were assigned to groups receiving: (1) 80 mg/kg/day methylprednisolone (MP80) intramuscularly for 1, 2, and 3 days; (2) 10 mg/kg/day methylprednisolone (MP10, pulse-dose) for 3 days; or (3) saline (placebo) for 3 days; and (4) a control group. Diaphragmatic in vitro force-frequency and force-velocity relationships, myosin heavy chain (MyHC) isoform protein and mRNA, insulin-like growth factor-1 (IGF-1), muscle atrophy F-box (MAF-box) mRNA, and volume density of abnormal myofibrils were measured at each time-point. MP80 did not affect animal nutritional state or fiber cross-sectional area as assessed in separate pair-fed groups receiving methylprednisolone or saline for 3 days. Compared with control values, MP80 decreased diaphragmatic maximum tetanic tension (Po) by 19%, 24%, and 34% after 1, 2, and 3 days (P < 0.05), respectively, whereas MP10 decreased Po modestly (12%; P > 0.05). Vmax and MyHC protein proportions were unchanged in both the MP80 and MP10 groups. Maximum power output decreased after 2 and 3 days of MP80. Suppression of IGF-1 and overexpression of MAF-box mRNA occurred in both MP groups. Significant myofibrillar disarray was also observed in both MP groups. The decline in Po was significantly associated with the increased volume density of abnormal myofibrils. Thus, very high-dose methylprednisolone (MP80) can produce rapid reductions in diaphragmatic function, whereas pulse-dose methylprednisolone (MP10) produces only modest functional loss.

Potential advantages of patient-ventilator synchrony.

During conventional mechanical ventilation, fixed set pressure, flow, and tidal volume result in a mismatch between patient and ventilator inspiratory time and in a patient's inability to adapt to changing ventilatory demand. Synchrony between the patient and ventilator improves neuromuscular coupling and the ability to adapt to increased ventilatory demand or loading. The sensation of dyspnea prevents ineffective inspiratory efforts and attenuates periodic breathing during sleep.

Early effects of mechanical ventilation on isotonic contractile properties and MAF-box gene expression in the diaphragm.

This study aimed to determine the time-dependent effects of diaphragmatic inactivity on its maximum shortening velocity (V(max)) and the muscle atrophy F-box (MAF-box, atrogin-1) gene expression during controlled mechanical ventilation (CMV). Twenty-four New Zealand White rabbits were grouped into 1 day, 2 days, and 3 days of CMV and controls in equal numbers. The in vitro isotonic contractile properties of the diaphragm were determined. In addition, myosin heavy chain protein and mRNA, myosin light chain, MAF-box mRNA, and volume density of abnormal myofibrils were measured. Tetanic force decreased, and V(max) increased from control of 6.4 to 6.6, 7.7, and 8.1 muscle lengths per second after 1, 2, and 3 days of CMV, respectively (P < 0.02). The increased V(max) compensated for the decreased tetanic force; consequently, compared with the controls, maximum power output was unchanged after 3 days of CMV. V(max) correlated with the volume density of abnormal myofibrils [y = 0.1x + 5.7 (r = 0.87, P < 0.01)]. In the diaphragm, MAF-box was overexpressed (355% of control) after 1 day of CMV, before the evidence of structural myofibril disarray. In conclusion, CMV produced a time-dependent increase in V(max) that was associated with the degree of myofibrillar disarray and independent of changes in myosin isoform expression. Furthermore, CMV produced an increase in MAF-box mRNA levels that may be partially or completely responsible for the degree of myofibrillar disarray resulting from CMV.