Airway Pressure Release Ventilation (APRV) for the Treatment of Severe Life-Threatening ARDS in a Morbidly Obese Patient

Airway pressure release ventilation (APRV) is a relatively new mode of ventilation that became commercially available in the United States in the mid-1990s. APRV differs fundamentally from that of conventional positive-pressure ventilation. Whereas conventional modes of ventilation begin the ventilatory cycle at a baseline pressure and elevate airway pressure to accomplish tidal ventilation, APRV commences at an elevated baseline pressure and follows with a deflation to accomplish tidal ventilation (Figure 1) [1]. The elevated baseline pressure facilitates oxygenation and lung recruitment while the timed releases aids in carbon dioxide removal. Advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle and decreased need for sedation. APRV is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. APRV is a recognized mode of ventilation in trauma patients with acute respiratory distress syndrome (ARDS) [2]. However, its adoption in the medical ICU has been limited. We report the case of a morbidly obese patient who developed aspiration pneumonitis and severe life-threatening ARDS who was successfully managed with APRV.

Case report
A 25 year-old African-American male presented to hospital for ophthalmic surgery for retinal detachment of his right eye. His past medical history was signifi cant for asthma, morbid obesity (BMI of 53.2 kg/m2), and obstructive sleep apnea. During anesthesia his airway was “secured” with a laryngeal mask (LMA). In the immediate post-operative period, he developed respiratory distress which was treated with supplemental oxygen as well as methylprednisolone, furosemide, and nebulized bronchodilators. He was transferred to the medical intensive care unit (MICU) with respiratory distress, progressive hypoxemia and hypotension requiring fl uid resuscitation and endotracheal intubation (approximately 6 hours after surgery) with assisted mechanical ventilation. On presentation to the ICU his temperature was 98oF, heart rate 120 beats per minute, blood pressure 90/60 mmHg, respiratory rate 30 breaths per minute with an oxygen saturation of 88% on a rebreathing mask. Physical examination was notable for morbid obesity, coarse breath sounds on lung auscultation and bilateral lower extremity pitting edema. On admission white blood cell was 31x109/l with 90% neutrophils, creatinine was 2.1 mg/dl and lactate was 6.7 mmol/l (67.4 mg/dl). Arterial blood gas analysis on assistcontrolled ventilation with a tidal volume 750 ml (9 ml/kg ideal body weight of 80kg), respiratory rate of 20/minute, PEEP of 5 cmH2O and FiO2 of 1.0 was pH 7.22, PaCO2 58 mmHg and PaO2 of 82 mmHg with an oxygen saturation of 94%. The chest radiograph revealed diffuse bilateral alveolar airspace disease (Figure 2). The presumptive diagnosis was acid aspiration pneumonitis causing ARDS (Mendelsohn’s syndrome) [3]. The patient developed progressive hypoxia despite increasing PEEP to 16 cmH2O with repeat blood gas analysis demonstrating a pH of 7.21, PaCO2 of 49 mmHg, PaO2 of 50 mmHg with an oxygen saturation of 84%. At this point the patient was switched to APRV (Puritan-Bennett 940® ventilator) with the following settings: PEEP-high 35 cmH2O, PEEP-low 5 cmH2O, release rate of 12/minute, time-low of 0.8 s, pressure support of 5 cmH2O above PEEP-high and a FiO2 of 100%. Within hours of changing to APRV we noted signifi cant improvement in oxygenation, a decrease in dead space ventilation ratio from 0.7 to 0.46 (NICO® Vd/Vt) with minimal change in PaCO2. Repeat chest radiograph was markedly improved (Figure 3). The change in the PaO2/FiO2 and PaCO2 over time is illustrated in Figure 4. A transthoracic echocardiogram demonstrated normal cardiac size and function while lower extremity venous Doppler examination was normal. Additional treatment included a hydrocortisone infusion at 10 cc/hr (for 7 days followed by a steroid taper), enoxaparin at prophylactic dose (40 mg SC daily) and enteral nutrition (Oxepa, Ross/Abbott Laboratories, Chicago, IL). Vancomycin and piperacillin/tazobactam initiated for treatment of presumed sepsis were discontinued once the mini-bronchoalveolar lavage and all other cultures were negative. The patient had a prolonged stay in ICU, being liberated from mechanical ventilation after 13 days of APRV. The remainder of his hospital course was uneventful; he was discharged after 20 days of hospitalization.

Discussion
ARDS is a frequent cause of admission to the ICU. The current standard ventilatory mode for patients with ARDS is volume-controlled ventilation using a low-tidal volume lung protective strategy (6 ml/kg ideal body weight) [4]. In a subset of patients with severe ARDS such a ventilatory strategy may be unable to maintain adequate arterial oxygenation and ventilation. APRV has been used in trauma patients as a rescue mode to improve oxygenation in patients failing assist-control mode [2]. There is limited data on the use of APRV in medical patients with severe ARDS. APRV may be particularly useful in patient with morbid obesity. We believe that the use of APRV in our patient was a life saving intervention. APRV, fi rst described by Stock and Downs in 1987 [5], is a time-triggered, pressure-limited, time-cycled mode of ventilation that allows unrestricted spontaneous breathing throughout the entire ventilatory cycle. The patient’s spontaneous breaths are unrestricted and independent of the ventilator cycle. APRV helps to meet the goals of ARDS management by maximizing alveolar recruitment [6] while limiting the transalveolar pressure gradient and barotrauma. APRV is very well tolerated by patients allowing minimal sedation with spontaneous breathing which improves V/Q mismatching and cardiac performance [7,8]. The reduced need for sedative agents as compared to other modes of advanced ventilation is a very important attribute of APRV, as the use of sedative agents has been liked to prolonged ICU stays, delirium and ncreased risk of complications. Morbid obesity has signifi cant effects on the respiratory system which impacts the ventilatory management of these patients. The expiratory reserve volume (ERV) declines signifi cantly with increasing BMI. The fall in ERV is presumably due to small airway closure particularly in the dependent areas of the lung. The vital capacity (VC), total lung capacity (TLC) and functional residual volume (FRV) are generally maintained in otherwise normal individuals with mild to moderate obesity but are reduced by up to 30% in morbidly obese patients [9-10]. In addition, the mechanical effect of obesity causes a decrease in chest wall compliance. The effects of obesity on the respiratory system are compounded in patients with acute lung injury, consequently the standard approach to ventilatory support with low-tidal volumes may result in severe lung derecruitment and inadequate ventilation. APRV may be the ideal ventilatory mode in obese patients with severe ARDS as the increased mean alveolar pressure with short release time will recruit collapsed lung while preventing over-distension of ventilated alveoli. In our institution, we use a step-wise strategy to liberate patients from mechanical ventilation when on the APRV mode. First we decrease FiO2 followed by the PEEP-high. Should the patient tolerate the decrease in FiO2 and PEEP-high, we then increase time-low with further reductions in the PEEP-high until we reach a CPAP (PEEP-low) of 5 cmH2O. At this point we increase the pressure support to 10 cmH2O followed by extubation if the patient is comfortable on these settings. It is very important to stress that the PEEPhigh should be reduced in increments of no greater than 3 cmH2O at an interval no more frequently than every 8-12 hours. Severe (and irreversible) derecruitment may occur if PEEP-high is weaned to rapidly.
In summary, we believe that APRV should be considered in patients with severe ARDS who tolerate low-tidal volume assist controlled ventilation poorly. APRV may be particularly useful in the management of obese patients with ARDS.


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Fat Embolism Syndrome

The classical syndrome of fat embolism is characterized by the triad of respiratory failure, neurologic dysfunction and the presence of a petechial rash. Fat embolism syndrome (FES) occurs most commonly following orthopedic trauma, particularly fractures of the pelvis or long bones, however non-traumatic fat embolism has also been known to occur on rare occasions. Because no definitive consensus on diagnostic criteria exist, the accurate assessment of incidence, comparative research and outcome assessment is difficult. A reasonable estimate of incidence in patients after long bone or pelvic fractures appears to be about 3-5%. The FES therefore remains an important cause of morbidity and mortality and warrants further investigation and research to allow proper recognition as well as the development of preventive and therapeutic strategies. Early fracture fixation is likely to reduce the incidence of fat embolism syndrome and pulmonary complications; however the best fixation technique remains controversial.
The use of prophylactic corticosteroids may be considered to reduce the incidence of FES and in selected high-risk trauma patients but effects on outcome are not proved. New reaming and venting techniques have potential to reduce the incidence of FES during arthroplasty. Unfortunately, no specific therapies have been proven to be of benefit in FES and treatment remains supportive with priority being given to the maintenance of adequate oxygenation.


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Year in Review 2006: The Critically Ill Patient in the Pediatric ICU

The care of the critically ill patient in the pediatric intensive care unit (PICU) has remained an important topic for those health care providers dealing with children. The purpose of this article is to introduce to the reader a summary of selected papers which we consider relevant to the care of the pediatric critically ill patient and that were published in the year 2006. These articles were selected on the basis of application to the PICU, overall importance and are not to be solely considered authoritative in their field. There are many other useful articles. We have attempted to choose those articles with scientific merit and rigorous methodology that we believe present interesting data in the field.


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Effectiveness Study of rHuEPO in the ICU

Purpose: To evaluate the clinical outcomes and resource use in ICU patients receiving rHuEPO in a naturalistic setting. Methods: A retrospective, case-matched (1:2 ratio) study compared patients receiving rHuEPO to a control group. Patients admitted between January 2000 and July 2002 with an ICU length of stay (LOS) ¡Ý3 days were identifi ed by an electronic data repository. Patients, who received rHuEPO prior to ICU admission, had chronic renal failure or were <18 years of age were excluded. Patients were matched by age (¡À5 years), sex, admission year and ICU type. Collected data included patient demographics, admission date, ICU and hospital mortality and LOS, mechanical ventilation days, serum creatinine concentration, hemoglobin concentration, number of blood transfusions, and ICU resource use. Results: rHuEPO-treated patients (n=391) were matched with 782 controls. Patients receiving rHuEPO had higher Simplifi ed Acute Physiology Scores II (46.2 vs 38.8; p <0.001) and received signifi cantly more blood transfusions than control patients (19 vs 6; p <0.001). After adjusting for severity of illness in a linear regression model, rHuEPO was signifi cantly associated with increased blood transfusions and higher mortality risk. Patients receiving rHuEPO had signifi cantly longer hospital and ICU LOS, mechanical ventilation duration, and higher hospital and ICU mortality rate and hospital resource use (p <0.001). Conclusions: In this real-world retrospective analysis, critically ill patients treated with rHuEPO did not experience clinical benefi ts; however, patients were sicker and received rHuEPO late in their ICU stay. Monitoring prescribing patterns and patient selection of rHuEPO treatment in critically ill patients in clinical practice is recommended to optimize rHuEPO use and outcomes.


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Critical Care of the Liver Transplant ICU Patients: A Pittsburgh “Point of View”

The purpose of this review is to summarize the advances in critical care management of the liver transplant ICU patients (patients with end stage liver disease, before and after orthotopic liver transplant). The review is based on search of Medline literature, with a focus on liver failure patients and critical care issues around liver transplantation. Starzl Transplantation Institute at the University of Pittsburgh Medical Center is one of the global leaders in the treatment of end stage liver disease (ESLD). This review is in part based on our work in the 28-bed liver transplant ICU at Montefi ore Hospital, University of Pittsburgh Medical Center, in Pittsburgh, PA. Over the past few years, our understanding of the several important pathophysiologic markers of end stage liver disease has been signifi cantly improved. For example, we do now much better understand hyperdynamic circulation of liver failure, hepatorenal syndrome and its consequences, the role of TIPSS (transjugular intrahepatic portosystemic shunt) and adrenal insuffi ciency in liver failure patients. The management and prophylaxis of variceal bleeding and subacute bacterial peritonitis (SBP), has been successfully standardized. These and other advances in understanding of ESLD pathophysiology and its clinical results, have certainly contributed to more promising outcomes in the ICU management of these complex patients.


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Abdominal Sarcoidosis

Abdominal sarcoidosis is an uncommon form of sarcoidosis. The clinical presentation of esophageal, gastric, small bowel, colon, appendicular, spleen, pancreas, and abdominal aortic sarcoidosis are discussed in this review. The differential diagnosis of abdominal sarcoidosis is extensive. Other granulomatous diseases including tuberculosis, fungal infections, parasitic diseases, infl ammatory bowel disease, and Whipple’s disease should be excluded before making the diagnosis of gastrointestinal sarcoidosis. Corticosteroid therapy is the mainstay of medical therapy in abdominal sarcoidosis. Second line agents such as methotrexate are also discussed. Surgical intervention may be necessary in patients with bowel obstruction, perforation, or massive hemorrhage. The authors also provide their experience regarding preoperative pulmonary evaluation of patients with pulmonary sarcoidosis undergoing surgery.


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Severe Complications of Herbal Medicines

Herbal medicines are being increasingly used for treatment of variety of disorders. Herbal medicines are generally thought to lack severe side effects. Despite of the general belief, herbal medicines are known to cause serious side effects and toxicities. On the other hand, physicians’ knowledge of herbal medicines and their potential toxicities are generally limited. Neurotoxicity, cardiac toxicity, pulmonary toxicity, hepatotoxicity, and nephrotoxicity are potential severe complications of herbal medicines.


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Sublingual Capnometry: A Non-invasive Measure of Microcirculatory Dysfunction in Sepsis

Sepsis is among the most common reason for admission to intensive care units throughout the world. Sepsis is characterized by a generalized microcirculatory injury, which results in tissue dysoxia. Tissue dysoxia is believed to be the causation of multiorgan dysfunction syndrome (MODS) which commonly complicates the course of sepsis. The expedient detection and correction of tissue dysoxia may limit the development of MODS. The standard oxygenation and hemodynamic variables (blood pressure, arterial oxygenation, cardiac output) which are monitored in critically ill patients are “upstream” markers and provide little information as to the adequacy of tissue oxygenation. Global “downstream” markers of tissue dysoxia such as mixed venous oxygen saturation and blood lactate are insensitive indicators of the extent of the microcirculatory injury in patients with sepsis. Sublingual/buccal mucosal PCO2 is a regional marker of microvascular perfusion and tissue dysoxia that holds great promise for the risk stratifi cation and endpoint of goal-directed resuscitation in patients with sepsis.


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Cardiopulmonary Emergencies in Sarcoidosis

Sarcoidosis is a systemic disease that commonly involves the lungs and the heart. Although rare, lifethreatening cardiopulmonary emergencies can occur. Acute respiratory failure, massive hemoptysis, and cardiac emergencies are described in sarcoidosis. These clinical manifestations can be the first clinical presentation of sarcoidosis. The subject of cardiopulmonary sarcoidosis is reviewed.


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Clevidipine: A Unique Agent for the Critical Care Practitioner

Clevidipine is a new third generation intravenous dihydropyridine calcium channel blocker. It is a specific arterial vasodilator developed for the acute reduction and control of arterial blood pressure in the perioperative period. This drug has an extremely short half life and is rapidly metabolized by tissue and plasma esterases. Clevidipine is a potent arterial vasodilator with very little or no effect of the myocardial contractility and venous capacitance and also minimal side effects. Clevidipine can also theoretically help to protect against organ reperfusion injury. Theoretically, this effect resides in the capacity of this agent to debilitate oxygen free radical-mediated toxicity, cell calcium overload and augment endothelial nitric oxide bioavailability through antioxidative actions. As a result it may diminish the severity of low flow myocardial ischemia and preserve the coronary endothelial function thereby reducing the infarct size. Due to all the characteristics of this parenteral agent it promises to be the drug of choice for the critical care practitioner for the strict control of blood pressure in different clinical scenarios.


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