Capnography for Monitoring of the Critically Ill Patient.

Capnography has been widely adopted in multiple clinical areas. The capnogram and end-tidal carbon dioxide offer a wealth of information, in the right clinical setting, and when properly interpreted. In this article, the authors aim to review the most common clinical scenarios during which capnography has been shown to be of benefit. This includes the areas of fluid responsiveness, cardiopulmonary resuscitation, and conscious sedation. They review the published literature, highlighting its pitfalls and identifying its limitations.

Estimating Arterial Partial Pressure of Carbon Dioxide in Ventilated Patients: How Valid Are Surrogate Measures?

The arterial partial pressure of carbon dioxide (PaCO2) is an important parameter in critically ill, mechanically ventilated patients. To limit invasive procedures or for more continuous monitoring of PaCO2, clinicians often rely on venous blood gases, capnography, or transcutaneous monitoring. Each of these has advantages and limitations. Central venous Pco2 allows accurate estimation of PaCO2, differing from it by an amount described by the Fick principle. As long as cardiac output is relatively normal, central venous Pco2 exceeds the arterial value by approximately 4 mm Hg. In contrast, peripheral venous Pco2 is a poor predictor of PaCO2, and we do not recommend using peripheral venous Pco2 in this manner. Capnography offers measurement of the end-tidal Pco2 (PetCO2), a value that is close to PaCO2 when the lung is healthy. It has the advantage of being noninvasive and continuously available. In mechanically ventilated patients with lung disease, however, PetCO2 often differs from PaCO2, sometimes by a large degree, often seriously underestimating the arterial value. Dependence of PetCO2 on alveolar dead space and ventilator expiratory time limits its value to predict PaCO2. When lung function or ventilator settings change, PetCO2 and PaCO2 can vary in different directions, producing further uncertainty. Transcutaneous Pco2 measurement has become practical and reliable. It is promising for judging steady state values for PaCO2 unless there is overt vasoconstriction of the skin. Moreover, it can be useful in conditions where capnography fails (high-frequency ventilation) or where arterial blood gas analysis is burdensome (clinic or home management of mechanical ventilation).

Improving CPR Performance.

Cardiac arrest continues to represent a public health burden with most patients having dismal outcomes. CPR is a complex set of interventions requiring leadership, coordination, and best practices. Despite the widespread adoption of new evidence in various guidelines, the provision of CPR remains variable with poor adherence to published recommendations. Key steps health-care systems can take to enhance the quality of CPR and, potentially, to improve outcomes, include optimizing chest compressions, avoiding hyperventilation, encouraging intraosseous access, and monitoring capnography. Feedback devices provide instantaneous guidance to the rescuer, improve rescuer technique, and could impact patient outcomes. New technologies promise to improve the resuscitation process: mechanical devices standardize chest compressions, capnography guides resuscitation efforts and signals the return of spontaneous circulation, and intraosseous devices minimize interruptions to gain vascular access. This review aims at identifying a discreet group of interventions that health-care systems can use to raise their standard of cardiac resuscitation.

Capnography During Critical Illness.

Capnography has made steady inroads in the ICU and is increasingly used for all patients who are mechanically ventilated. There is growing recognition that capnography is rich in information about lung and circulatory physiology and provides insight into many diseases and treatments. These include conditions of impaired matching of ventilation and perfusion, such as pulmonary embolism and obstructive lung diseases; circulatory questions, such as the adequacy of chest compressions during cardiac arrest or fluid responsiveness in patients in shock; and the safety of procedural sedation. In this review, we emphasize analysis of the entire capnographic waveform as a way to glean additional useful information. We also discuss important limitations of capnography, especially when it is considered to be a surrogate for Paco2.

Impact of an intensive care unit telemedicine program on patient outcomes in an integrated health care system.

IMPORTANCE: Intensive care unit (ICU) telemedicine (TM) programs have been promoted as improving access to intensive care specialists and ultimately improving patient outcomes, but data on effectiveness are limited and conflicting. OBJECTIVE: To examine the impact of ICU TM on mortality rates and length of stay (LOS) in an integrated health care system. DESIGN, SETTING, AND PARTICIPANTS: Observational pre-post study of patients treated in 8 "intervention" ICUs (7 hospitals within the US Department of Veterans Affairs health care system) during 2011-2012 that implemented TM monitoring during the post-TM period as well as patients treated in concurrent control ICUs that did not implement an ICU TM program. INTERVENTION: Implementation of ICU TM monitoring. MAIN OUTCOMES AND MEASURES: Unadjusted and risk-adjusted ICU, in-hospital, and 30-day mortality rates and ICU and hospital LOS for patients who did or did not receive treatment in ICUs equipped with TM monitoring. RESULTS: Our study included 3355 patients treated in our intervention ICUs (1708 in the pre-TM period and 1647 in the post-TM period) and 3584 treated in the control ICUs during the same period. Patient demographics and comorbid illnesses were similar in the intervention and control ICUs during the pre-TM and post-TM periods; however, predicted ICU mortality rates were modestly lower for admissions to the intervention ICUs compared with control ICUs in both the pre-TM (3.0% vs 3.6%; P = .02) and post-TM (2.8% vs 3.5%; P < .001) periods. Implementation of ICU TM was not associated with a significant decline in ICU, in-hospital, or 30-day mortality rates or LOS in unadjusted or adjusted analyses. For example, unadjusted ICU mortality in the pre-TM vs post-TM periods were 2.9% vs 2.8% (P = .89) for the intervention ICUs and 4.0% vs 3.4% (P = .31) for the control ICUs. Unadjusted 30-day mortality during the pre-TM vs post-TM periods were 7.7% vs 7.8% (P = .91) for the intervention ICUs and 12.0% vs 10.2% (P = .08) for the control ICUs. Evaluation of interaction terms comparing the magnitude of mortality rate change during the pre-TM and post-TM periods in the intervention and control ICUs failed to demonstrate a significant reduction in mortality rates or LOS. CONCLUSIONS AND RELEVANCE: We found no evidence that the implementation of ICU TM significantly reduced mortality rates or LOS.

Abundant DNase I-sensitive bacterial DNA in healthy porcine lungs and its implications for the lung microbiome.

Human lungs are constantly exposed to bacteria in the environment, yet the prevailing dogma is that healthy lungs are sterile. DNA sequencing-based studies of pulmonary bacterial diversity challenge this notion. However, DNA-based microbial analysis currently fails to distinguish between DNA from live bacteria and that from bacteria that have been killed by lung immune mechanisms, potentially causing overestimation of bacterial abundance and diversity. We investigated whether bacterial DNA recovered from lungs represents live or dead bacteria in bronchoalveolar lavage (BAL) fluid and lung samples in young healthy pigs. Live bacterial DNA was DNase I resistant and became DNase I sensitive upon human antimicrobial-mediated killing in vitro. We determined live and total bacterial DNA loads in porcine BAL fluid and lung tissue by comparing DNase I-treated versus untreated samples. In contrast to the case for BAL fluid, we were unable to culture bacteria from most lung homogenates. Surprisingly, total bacterial DNA was abundant in both BAL fluid and lung homogenates. In BAL fluid, 63% was DNase I sensitive. In 6 out of 11 lung homogenates, all bacterial DNA was DNase I sensitive, suggesting a predominance of dead bacteria; in the remaining homogenates, 94% was DNase I sensitive, and bacterial diversity determined by 16S rRNA gene sequencing was similar in DNase I-treated and untreated samples. Healthy pig lungs are mostly sterile yet contain abundant DNase I-sensitive DNA from inhaled and aspirated bacteria killed by pulmonary host defense mechanisms. This approach and conceptual framework will improve analysis of the lung microbiome in disease.

Co-regulation of survival of motor neuron and Bcl-xL expression: implications for neuroprotection in spinal muscular atrophy.

Spinal muscular atrophy (SMA), a fatal genetic motor disorder of infants, is caused by diminished full-length survival of motor neuron (SMN) protein levels. Normally involved in small nuclear ribonucleoprotein (snRNP) assembly and pre-mRNA splicing, recent studies suggest that SMN plays a critical role in regulating apoptosis. Interestingly, the anti-apoptotic Bcl-x isoform, Bcl-xL, is reduced in SMA. In a related finding, Sam68, an RNA-binding protein, was found to modulate splicing of SMN and Bcl-xL transcripts, promoting SMNΔ7 and pro-apoptotic Bcl-xS transcripts. Here we demonstrate that Bcl-xL expression increases SMN protein by ∼2-fold in SH-SY5Y cells. Conversely, SMN expression increases Bcl-xL protein levels by ∼6-fold in SH-SY5Y cells, and ∼2.5-fold in the brains of transgenic mice over-expressing SMN (PrP-SMN). Moreover, Sam68 protein levels were markedly reduced following SMN and Bcl-xL expression in SH-SY5Y cells, suggesting a feedback mechanism co-regulating levels of both proteins. We also found that exogenous SMN expression increased full-length SMN transcripts, possibly by promoting exon 7 inclusion. Finally, co-expression of SMN and Bcl-xL produced an additive anti-apoptotic effect following PI3-kinase inhibition in SH-SY5Y cells. Our findings implicate Bcl-xL as another potential target in SMA therapeutics, and indicate that therapeutic increases in SMN may arise from modest increases in total SMN.

The flow-time waveform predicts respiratory system resistance and compliance.

PURPOSE: Knowledge of patients' lung compliance and resistance aids clinical management. We investigated whether these values, readily measured during volume assist-control ventilation (VACV), could also be estimated during pressure assist-control ventilation (PACV). METHODS: Data were collected in 12 mechanically ventilated human subjects. During VACV, peak pressure, plateau pressure, end-expiratory pressure, tidal volume, and inspiratory flow rate were measured. During PACV, inspiratory pressure, end-expiratory pressure, and tidal volume were recorded. The linear component of the pressure-time waveform was extrapolated to time and flow axes. Using the equation of motion for the respiratory system, assuming a nonlinear resistance, we calculated inspiratory resistance and compliance. During VACV, compliance and inspiratory resistance were calculated in the conventional manner. RESULTS: In ventilated subjects, mean compliance during PACV was 37.06 ± 15.65 mL/cm H(2)O, and during VACV, 36.93 ± 12.18 mL/cm H(2)O. Mean inspiratory resistance during PACV was 15.17 ± 5.14 cm H(2)O/L per second, whereas during VACV, it was 12.50 ± 2.99 cm H(2)O/L per second. A strong correlation is evident between compliance and inspiratory resistance calculated during PACV vs VACV (r(2) of 0.73 and 0.51, respectively). CONCLUSIONS: During PACV, the inspiratory flow waveform is linear, and its slope contains information regarding inspiratory resistance and compliance. Calculated values correlate with those during VACV.

The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. The most common CF-associated mutation is ΔF508, which deletes a phenylalanine in position 508. In vitro studies indicate that the resultant protein, CFTR-ΔF508, is misprocessed, although the in vivo consequences of this mutation remain uncertain. To better understand the effects of the ΔF508 mutation in vivo, we produced CFTR(ΔF508/ΔF508) pigs. Our biochemical, immunocytochemical, and electrophysiological data on CFTR-ΔF508 in newborn pigs paralleled in vitro predictions. They also indicated that CFTR(ΔF508/ΔF508) airway epithelia retain a small residual CFTR conductance, with maximal stimulation producing ~6% of wild-type function. Cyclic adenosine 3',5'-monophosphate (cAMP) agonists were less potent at stimulating current in CFTR(Δ)(F508/)(Δ)(F508) epithelia, suggesting that quantitative tests of maximal anion current may overestimate transport under physiological conditions. Despite residual CFTR function, four older CFTR(ΔF508/ΔF508) pigs developed lung disease similar to human CF. These results suggest that this limited CFTR activity is insufficient to prevent lung or gastrointestinal disease in CF pigs. These data also suggest that studies of recombinant CFTR-ΔF508 misprocessing predict in vivo behavior, which validates its use in biochemical and drug discovery experiments. These findings help elucidate the molecular pathogenesis of the common CF mutation and will guide strategies for developing new therapeutics.

Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells.

Spinal muscular atrophy (SMA), a neurodegenerative disorder primarily affecting motor neurons, is the most common genetic cause of infant death. This incurable disease is caused by the absence of a functional SMN1 gene and a reduction in full length survival of motor neuron (SMN) protein. In this study, a neuroprotective function of SMN was investigated in differentiated human SH-SY5Y cells using an adenoviral vector to over-express SMN protein. The pro-survival capacity of SMN was assessed in an Akt/PI3-kinase inhibition (LY294002) model, as well as an oxidative stress (hydrogen peroxide) and excitotoxic (glutamate) model. SMN over-expression in SH-SY5Y cells protected against Akt/phosphatidylinositol 3-kinase (PI3-kinase) inhibition, but not oxidative stress, nor against excitotoxicity in rat cortical neurons. Western analysis of cell homogenates from SH-SY5Y cultures over-expressing SMN harvested pre- and post-Akt/PI3-kinase inhibition indicated that SMN protein inhibited caspase-3 activation via blockade of calpain-mediated procaspase-3 cleavage. This study has revealed a novel anti-apoptotic function for the SMN protein in differentiated SH-SY5Y cells. Finally, the cell death model described herein will allow the assessment of future therapeutic agents or strategies aimed at increasing SMN protein levels.

Breast screening in the emerging world: high prevalence of breast cancer in Cairo.

The Cairo Breast Screening Trial (CBST) was designed to evaluate the role of clinical breast examination as a primary screening modality in the context of primary care, as in Egypt breast cancer is usually diagnosed at an advanced stage. A specialised medical centre in Cairo (the Italian Hospital) was selected as the headquarters of the study. The initial target group was women age 35-64 living in a geographically defined area around the Italian Hospital, 4116 being contacted by social workers and invited to attend a Primary Health Centre for clinical breast examination. High rates of breast cancer were observed; 8 per 1000 at the first examination and approximately 2 per thousand among those who attended for re-screening. The initial prevalence suggests that many women in the community with early but palpable breast cancer fail to seek medical attention until their cancer is advanced. The detection rate on re-screening, and after follow-up of those who only received one or no screens, ( approximately 3/1000) is similar to expectation.

Effect of protein energy malnutrition (PEM) on spermatogenesis in rat testis.

In this work 60 male albino rats were subjected to a feeding experiment aimed to study the influence of protein free and reduced diets on normal function of rat testes. It was shown that the PEM exerts adverse effects on testicular function, the nature and severity of these effects depend on the duration of the deficiency state. Histological examination of rat testis, revealed that the spermatogenesis is arrested at spermatogonium stage in rats fed on protein free diet, and at primary and secondary spermatocyte stage in rats fed on normal but reduced diet.

Familial male hermaphroditism.

One of the main objectives of a study of intersex conditions in infancy and childhood was an early decision on the sex of rearing. The present study emphasizes the importance of combined clinical, genetic and pathologic studies for proper management. The described families are the first reported Egyptian cases with familial male hermaphroditism.