Deviation from Clinical Routines Can Reveal Sources of Device Design Vulnerability.

The ability to adequately ventilate a patient is critical and sometimes a challenge in the emergency, intensive care, and anesthesiology settings. Commonly, initial ventilation is achieved through the use of a face mask in conjunction with a bag that is manually squeezed by the clinician to generate positive pressure and flow of air or oxygen through the patient's airway. Large or small erroneous openings in the breathing circuit can lead to leaks that compromise ventilation ability. Standard procedure in anesthesiology is to check the circuit apparatus and oxygen delivery system prior to every case. Because the face mask itself is not a piece of equipment that is associated with a source of leak, some common anesthesia machine designs are constructed such that the circuit is tested without the mask component. We present an example of a leak that resulted from complete failure of the face mask due to a tiny tear in its cuff by the patient's sharp teeth edges. This subsequently prevented formation of a seal between the face mask and the patient's face and rendered the device incapable of generating the positive pressure it is designed to deliver. This instance depicts the broader lesson that deviation from clinical routines can reveal unappreciated sources of vulnerability in device design.

Even the Simplest Devices May Malfunction: Split Septum Design Revisited.

Split septum medical devices are used in tubing for intravenous (IV) fluid administration-an extremely common clinical task. These tubing caps contain a needleless, valveless system that allows fluid to flow directly through the lumen of the catheter but prevents backflow of fluid or blood when the tubing extension is not connected. We experienced complete failure of a needle-free connector extension set with a Luer-access split septum device in multiple patients due to the split septum remaining fused and essentially unsplit despite being connected on both ends. This led to an adverse event in a patient due to repeated unnecessary IV insertion attempts. This case shows how even the simplest of devices can malfunction and highlights the need for vigilance in clinical practice.

The critically ill patient with ataxia-telangiectasia: a case series.

OBJECTIVE: To describe the presentation, clinical course, and outcomes of critically ill patients with ataxia-telangiectasia. DESIGN: Retrospective case series. SETTING: Adult and pediatric intensive care units at an urban tertiary academic center. PATIENTS: Seven consecutive patients with confirmed diagnosis of ataxia-telangiectasia had nine intensive care admissions between January 1995 and December 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age at time of admission 15.9 yrs (median, 13.9 yrs; range, 7.3-33.9 yrs). Mean duration of intensive care unit stay was 17 days (median, 9 days; range, 2-39 days). The most common admitting diagnosis was respiratory distress (six of seven patients). There was no difference in ventilator settings or duration of intensive care unit stay between survivors and nonsurvivors (p > .05). Forty-three percent (three of seven patients) survived to intensive care unit discharge with a 3-yr survival that was 14% (one of seven patients). CONCLUSIONS: Critically ill patients with ataxia-telangiectasia have complex, multisystem diseases. In this case series, the most common intensive care unit admission diagnosis was respiratory failure. Suspected or confirmed bacterial infections were prevalent. Neuropathologic autopsy findings were similar to those previously reported. Special considerations for the critical care of patients with ataxia-telangiectasia are discussed.

Anesthetic and perioperative risk in the patient with Ataxia-Telangiectasia.

OBJECTIVES/AIM: To report our relatively large experience with perioperative care for patients with Ataxia-Telangiectasia (A-T) and to identify the nature and frequency of complications. BACKGROUND: Ataxia-Telangiectasia is a rare autosomal recessive genetic disorder resulting in progressive multisystem degeneration and characteristic findings including complex neurodegeneration, immunodeficiency, increased risk of malignancy, and lung disease. Anecdotal reports have suggested high perioperative morbidity in patients with A-T, but few data exist. METHODS/MATERIALS: The Ataxia-Telangiectasia Clinical Center database was cross-referenced with operative records between 1995 and 2009 to identify patients with perioperative A-T, and medical records were reviewed for preoperative history, management techniques, and complications. RESULTS: Twenty-one patients with A-T underwent 34 anesthetics during the study period. The median age was 12.5 years (range 6-33 years). Common comorbidities included neurologic (100%), pulmonary (68%), immunologic (50%), oncologic (47%), and gastroenterologic (35%) disorders. Supplemental oxygen was required on postanesthesia care unit discharge for 24% of patients with a maximal duration of 24 h. Although mild postoperative hypothermia was relatively common (44% of anesthetics), there were no major complications, no unplanned admissions, and no mortality in this series. CONCLUSIONS: Although limited by its retrospective nature, this is the first series describing perioperative risk for patients with A-T. Our results indicate that general anesthesia, airway manipulation, and perioperative mechanical ventilation may be tolerated with only minor postoperative anesthetic concerns. Perioperative providers should be aware of the complex multisystem medical concerns that may arise in these patients.

Respiratory decompensation with proning - when prone positioning can worsen respiratory mechanics.

Prone positioning recently gain- ed more popularity from its use in COVID-19 management. It is gene--rally considered to improve respiratory mechanics via increased lung compliance. In surgery, prone positioning is typically encountered when it is a necessity to access certain posterior anatomic structures. Though certain post-operative complications from prone positioning are well known (e.g., postoperative vision loss), the potential intraoperative complications that it can have for respiratory com-pliance and O2 saturation, in the setting of general anaesthesia, are perhaps less familiar, as only a few studies showed improved respiratory mechanics in the setting of ge-neral anaesthesia [1-3] and one study showed that prone positioning led to a 30-35% drop in respiratory compliance under general anaesthesia [4]. As the following case illustrates, proning is a critical point in the intraoperative course as it can sometimes lead to negative respiratory sequelae disrupting homeostasis.

Enhanced Recovery After Surgery (ERAS) protocols for spine surgery - review of literature.

Enhanced Recovery After Surgery (ERAS) is a multidisciplinary approach that uses a combination of evidence-based methods to improve patient care. Different ERAS protocols are used in various surgical fields but for spine surgery there is no widely used standard ERAS protocol. We compiled and examined the multiple available publications on ERAS protocols for spine surgery. Some general commonalities exist between ERAS protocols; however, a great deal of variety is observed in the granularity of important details such as differing drug choices or specific dosing. To assess and relate the different available ERAS protocols, we conducted a comprehensive narrative literature review focused on comparing commonalities and differences among the following aspects of ERAS protocols: mechanisms of action, post-surgery pain levels, opioid consumption, utilization of muscle relaxants, use of anti-inflammation drugs, and ambulation after surgery. Our goal in this project was to simplify the search process for institutions who review the literature. In this review, certain ERAS elements such as early ambulation, blood loss, pain management, and patient positioning are further explored in more depth.

A sudden presentation of abdominal compartment syndrome.

Abdominal compartment syndrome (ACS) is defined as sustained intra-abdominal pressure (IAP) exceeding 20 mm Hg, which causes end-organ damage due to impaired tissue perfusion, as with other compartment syndromes [1, 2]. This dysfunction can extend beyond the abdomen to other organs like the heart and lungs. ACS is most commonly caused by trauma or surgery to the abdomen. It is characterised by interstitial oedema, which can be exacerbated by large fluid shifts during massive transfusion of blood products and other fluid resuscitation [3]. Normally, IAP is nearly equal to or slightly above ambient pressure. Intra-abdominal hypertension is typically defined as abdominal pressure greater than or equal to 12 mm Hg [4]. Initially, the abdomen is able to distend to accommodate the increase in pressure caused by oedema; however, IAP becomes highly sensitive to any additional volume once maximum distension is reached. This is a function of abdominal compliance, which plays a key role in the development and progression of intra-abdominal hypertension [5]. Surgical decompression is required in severe cases of organ dysfunction - usually when IAPs are refractory to other treatment options [6]. Excessive abdominal pressure leads to systemic pathophysiological consequences that may warrant admission to a critical care unit. These include hypoventilation secondary to restriction of the deflection of the diaphragm, which results in reduced chest wall compliance. This is accompanied by hypoxaemia, which is exacerbated by a decrease in venous return. Combined, these consequences lead to decreased cardiac output, a V/Q mismatch, and compromised perfusion to intra-abdominal organs, most notably the kidneys [7]. Kidney damage can be prerenal due to renal vein or artery compression, or intrarenal due to glomerular compression [8] - both share decreased urine output as a manifestation. Elevated bladder pressure is also seen from compression due to increased abdominal pressure, and its measurement, via a Foley catheter, is a diagnostic hallmark. Sustained intra-bladder pressures beyond 20 mm Hg with organ dysfunction are indicative of ACS requiring inter-vention [2, 8]. ACS is an important aetiology to consider in the differential diagnosis for signs of organ dysfunction - especially in the perioperative setting - as highlighted in the case below.

Human life cost in anaesthesiology cost-benefit decisions.

The United States (US) aviation industry provides a potentially useful mental model for dealing with certain cost-benefit decisions in aesthesiology. The Federal Aviation Administration (FAA), the national aviation authority of the United States, quantifies a price for the value of a human life based on the U.S. Department of Transportation's (DOT) value of a statistical life (VSL) unit. The current VSL is around $9.6 million, indexed to grow with consideration given to inflation and wage changes from the 2016 baseline of $9.4 million [1]. To illustrate the concept, if the FAA estimates that 100 people are likely to die in the future given the current practice standards then the monetary cost of this loss will be $940 million. The FAA uses this estimated monetary value as an official reference point in its regulatory decisions, and the agency publishes in detail how it derives the estimated value. When proposing new regulations, the FAA bases its decisions on comparisons of the human life cost associated with the existing regulation versus the alternative cost that the industry stakeholders will incur subsequent to the adoption of the regulation. In this example, if the cost incurred by the industry is more than the $940 million cost then the FAA will not adopt the proposed regulation and hence will not require the industry to undertake this cost.

Docetaxel associated pathways in cisplatin resistant head and neck squamous cell carcinoma: a pilot study.

PURPOSE: This is a pilot study to identify changes in gene and protein expressions after treatment with docetaxel in cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). METHODS: Two cisplatin-resistant HNSCC cell lines, HN30 and HN12, were treated with either docetaxel or cisplatin. After 48 hours, differential gene expression between the two treatment groups (docetaxel-treated cells and cisplatin-treated cells) was analyzed using cDNA microarray. Differential protein expression between these two treatment groups was determined using PowerBlot and Western Blot analysis RESULTS: A total of 150 genes and proteins were found to have differential expression patterns in HNSCC after treatment with docetaxel versus cisplatin. Many of these differentially expressed genes and proteins were involved in the cell cycle (decreased E2F), apoptosis (increased bax), angiogenesis (increased thrombospondin), and signal transduction (decreased epidermoid growth factor receptor) regulatory pathways. CONCLUSIONS: Gene and protein expression are different and distinct between cells treated with docetaxel and cells treated with cisplatin. This finding provides evidence that different molecular pathways leading to cell death are targeted by docetaxel and cisplatin. Future studies focusing on these differentially expressed genes and proteins may improve our understanding, at the molecular level, of the mechanisms responsible for docetaxel-induced apoptosis in cisplatin-resistant HNSCC. Furthermore, these differentially expressed genes and proteins can be exploited as useful surrogate endpoint biomarkers in future clinical trials using docetaxel.

Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography.

Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 microg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium.

BACKGROUND: While the rejection of heterotopic tracheal allografts is characterized by complete airway obliteration, the rejection of orthotopic allografts leads to airway edema and cellular infiltrate of the lamina propria, but is not associated with obliteration. We hypothesized that orthotopic tracheal allografts undergo reepithelialization with recipient-derived mucosa and that this process prevents airway obliteration. METHODS: Thirty mice were randomly assigned to 6 experimental groups. BALB/c donor tracheal segments were transplanted orthotopically or heterotopically into syngeneic BALB/c or major histocompatability mismatched allogeneic C57BL/6 recipients. Recipients of allogeneic grafts were divided into a nonimmunosuppression group and an immunosuppression group (cyclosporine, 7 mg/kg per day). Twenty-one days after transplantation, histological assessment, immunohistochemistry for CD4 and CD8 lymphocyte infiltration and major histocompatibility-specific immunohistochemistry were performed on the grafts to assess rejection and donor or recipient origin of tissue. RESULTS: Untreated heterotopic allografts underwent complete airway obliteration by day 21. This response was prevented with cyclosporine immunosuppression. Untreated orthotopic allografts, however, demonstrated edema and lymphocytic infiltrate of the lamina propria resulting in clinical stridor without airway obliteration. Immunosuppressed orthotopic allografts did not develop edema or infiltrate of the lamina propria and consequently stridor did not occur. Immunohistochemical analysis demonstrated migration of recipient-derived mucosa into the donor allograft segment in both the untreated and treated orthotopic groups. CONCLUSIONS: Airway obliteration characteristic of rejecting heterotopic tracheal allografts does not occur in the orthotopic allografts. Migration of recipient mucosa into the donor allograft appears to prevent airway obliteration in the orthotopic allografts. These findings suggest that the orthotopic tracheal transplantation model more accurately represents the biological behavior of clinical tracheal allografts than the traditional heterotopic model.