Maryland CC Project

Dr. Nader Habashi is a master of all things APRV. What’s the evidence for APRV? Should APRV be used as a preventative mode of mechanical ventilation in patients at risk for ARDS rather than a salvage mode? In this review Dr. Habashi will give an overview of APRV, it’s role in low tidal volume ventilation, and also discuss some of the clinical controversies surrounding ventilator management in patients with ARDS. Airway Pressure Release Ventilation * Mode of mechanical ventilation that provides higher levels of PEEP with regular, brief releases in airway pressure. * Time-triggered, pressure-limited, time-cycled mode of ventilation * Allows patient to spontaneous ventilate (clear CO2) while also oxygenate through high PEEP APRV Concepts * The “Baby Lung” concept * Patients with severe ARDS have a decreased aeratable portion of lung (due to alveolar filling) * Goal is to increase recruitment, which should effectively increase area for alveolar ventilation. * Oxygenation can occur passively, so the more you recruit – the more you can oxygenate * Concept of alveolar interdependence * Low tidal volume ventilation (via volume control mechanical ventilation), in the ineffectively recruited lung may actually over distend surrounding alveoli causing more stretch injury. * Micro vs. Macro ventilation injury. * The distribution of the prescribed tidal volumes is what matters most. * APRV as a preventative mode of ventilation * In patients with ALI, reducing the incidence of derecruitment may be more effective in preventing the progression of disease. * Distribution of lung water is important.  If you can reduce the amount of edema within alveoli, prevent the exudative phase of ARDS from occurring, you may be able to prevent later complications such as cellular proliferation and pulmonary fibrosis.   References * Roy S, Habashi N, Sadowitz B, et al. Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury. Shock. 2013;39(1):28-38.[PubMed] * Andrews PL, Shiber JR, Jaruga-killeen E, et al. Early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: a systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg. 2013;75(4):635-41. [PubMed] * Frawley PM, Habashi NM. Airway pressure release ventilation and pediatrics: theory and practice. Crit Care Nurs Clin North Am. 2004;16(3):337-48, viii. [PubMed]

About a month ago, a young woman by the name of Angela Knight reached out to let us to let us know that she believes the use of the thrombelastogram (TEG) saved her life.  We were intrigued to say the least. Angela was preparing to give birth to her second son when she suddenly went into acute respiratory failure, a brief cardiac arrest, then subsequently progressed to DIC. This all took place at Memorial Hospital in South Bend, Indiana – the home of Dr. Mark Walsh and Dr. Maury Hurwich. Dr. Walsh is no stranger to the Maryland CC Project and is a proud enthusiast of the TEG.  Dr. Hurwich is an anesthesiologist at Memorial who has also played a major role in bringing the TEG to the bedside and incorporating it into hospital wide resuscitation protocols. Dr. Walsh’s suggested TEG based – goal directed blood component therapy based on work by Holcomb & Tapia. So what do you think?  Is the TEG ready for all forms of hemorrhagic shock & coagulopathy?  Tell us your thoughts below!   Just so everyone knows, we do not have any disclosures with the TEG or any corporate ties.  We do this for free.  We love good medicine. Suggested Reading * Walsh M, Jbara M, et al. Thromboelastographic goal-directed blood component therapy for severe hemorrhage. Blood Bulletin. March, 2014. * Jansen AJ, Van rhenen DJ, Steegers EA, Duvekot JJ. Postpartum hemorrhage and transfusion of blood and blood components. Obstet Gynecol Surv. 2005;60(10):663-71. * Gist RS, Stafford IP, Leibowitz AB, Beilin Y. Amniotic fluid embolism. Anesth Analg. 2009;108(5):1599-602. * Burtelow M, Riley E, Druzin M, Fontaine M, Viele M, Goodnough LT. How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol. Transfusion. 2007;47(9):1564-72. * Thachil J, Toh CH. Disseminated intravascular coagulation in obstetric disorders and its acute haematological management. Blood Rev. 2009;23(4):167-76. * Tapia NM, Chang A, Norman M, et al. TEG-guided resuscitation is superior to standardized MTP resuscitation in massively transfused penetrating trauma patients. J Trauma Acute Care Surg. 2013;74(2):378-85. * Holcomb JB, Minei KM, Scerbo ML, et al. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg. 2012;256(3):476-86.

Dr. Roy Brower is one of the original ARDSnet authors that brought Low Tidal-Volume ventilation to the masses.  We asked him to speak his mind on what he thinks we should do once the traditional ARDSnet goals no longer apply. Evidence behind ARDSnet protocol and beyond * EXPRESS PEEP Trial * Raise PEEP until Pplat = 28-30 * No mortality benefit, improved lung function, and reduced the duration of mechanical ventilation * High vs. Low PEEP in ALI Meta-analysis * Higher PEEP associated with improved survival among the subgroup of patients with ARDS * PaO2/FiO2 < 200 * Neuromuscular blockade for 48 hours * Improved 90 day survival * Reduced time off ventilator * PaO2/FiO2 < 150 * Used cisatracurium x 48 hours * Proning WORKS * Minimal cost intervention * Proned for 16 hours, supine for 6 hours * Decreased 28-day and 90-day mortality What else should you consider with a high Plateau Pressure? * We actually have no idea what the best Pplat is for each patient * The lungs are surrounded by a number of different variable forces, that contribute to the plateau pressure * Abdominal pressure (estimated by bladder pressure) * Force of the chest wall, thoracic cavity on the lungs * Pleural effusions * Pneumothorax * Lung diseases * Are you measuring the Pplat correctly? * Don’t be fooled, the real plateau can appear to be falsely elevated if the patient is making an inspiratory effort at the end of your end-inspiratory hold.  Look at the waveform!! Troubleshooting a Pplat > 30 * Check to see if the patient is a PEEP responder (Lower the PEEP) * Stop worry about it! (as long as you can justify the higher Pplat based on the above variables) * Lower the VT to < 4 cc/kg IBW – Mechanically vented patients rarely die from a high PaCO2 * We probably should stop using the Oscillator – Reason 1, Reason 2 Problem 2: What about ECMO? * Rationale makes sense * Not completely clear if ECMO is any better * The clinical trials need to be done to prove mortality/safety benefit References * Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8. * Hager DN, Krishnan JA, Hayden DL, Brower RG. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med. 2005;172(10):1241-5. * Grasso S, Stripoli T, De michele M, et al. ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure. Am J Respir Crit Care Med. 2007;176(8):761-7.

Today we are pleased to welcome a very prestigious guest: Dr. Mary Njoku, owner of the M. Jane Matjasko Professorship for Education in Anesthesiology, the current director of the University of Maryland Anesthesiology Residency Program, and currently acting as the Vice Chair of Education at the University of Maryland School of Medicine. Today she has taken time out of her VERY busy schedule to discuss a topic very near and dear to her heart: how to take care of the sick post-op patient once they arrive in the ICU. She has amassed a great deal of personal experience on the topic and can teach you in one hour what many people fail to learn in an entire lifetime of errors! Pearls * The handover from the OR to the ICU is the MOST important time in the post-op patients hospital course * Make sure your plan matches the operative teams * Identify mutual targets of resuscitation and support * Identify the pre-hospital and pre-procedure baseline in order to obtain a reasonable target of care * Evaluated both the operative note and the anesthesia log * Focus on any difficulties, focusing on the airway note and evaluate for any anomalies * Look for any resuscitation medications or fluids given (especially blood products) * Be aware of early signs of aggitation and delerium * Develop a scale to monitor * Be agressive with therapy * Focus on risk reduction- Important areas of risk reduction (SCIP: Surgical Care Improvement Project):  * Difficult airway? * If in doubt, never be afraid to extubate in the OR– more hands means more help! * Always gauge your skills- you are your best critic * Use the operative intubation note as a guide to the BEST case scenario possible * Equipment: make sure to have access to anything and everything you might need * Fiberoptic scopes, LMAs, bougies, etc…. * Fluid management: all patients are “positive” right after surgery * Insensible losses are often under-recognized * Need a consistent way to assess post-op fluid status * Post-op patients have limited reserve, so even minor fluctuations can be important * The ONLY way to catch post-op complications: serial re-examinations! * A handy tool for evaluating the risk of post-operative complications is using the Surgical Apgar Score (taken from Gawande et al. J Am College of Surgery 2007:204(2):201-208   References * Hockstein, MJ, Johnson LS. General Principles of Postoperative Intensive Care Unit Care from Critical Care Medicine: Principles of Diagnosis and Management in the Adult. ed: Parillo JE and Dellinger P. 2014 Elsevier 4th Edition. * Bird R, Nesbitt I. Postoperative care and analgesia in vascular surgery. Anaesthesia & Intensive Care Medicine 2013;14(5):197-199. * Diaz GC, Wagener G, Renz JF. Postoperative Care/Critical Care of the Transplant Patient. Anesthesiology Clinics 2013;31(4):723-735.

Dr. Burton Lee returns to MarylandCCProject to discuss the second half of his deeper dive into numeracy of the medical literature (“deep dive” is a bit of a stretch for him, but for us – there’s fractions involved…. FRACTIONS)!  All kidding aside, we are always grateful to spend time with Dr. Lee and lucky to have him teach us how sift through the morass of literature guiding our medical decision making. Pearls Causes for medical literature reversal * Poor methodology (RCTs, meta-analyses, quantitative reviews, etc.) * Conflict of interest * Innumeracy with the medical literature *** Core concepts of numeracy continued… * Law of small numbers:  Relative statistics (such as percentages) can be misleading with small sample sizes. * Regression to the mean:  The most likely outcome for any test is the average result.  Clinical relevance: The outcome of an intervention may not actually make an actual difference, only a perceived difference if the experimental group is different from the true mean. Also known as the gambler’s fallacy. * Apparently effective vs. Actually effective:  Remember, even if a perfect RCT shows a significantly positive finding, it is only reporting an apparently effective result.  When taking into account both alpha & beta error, the chance a paper is reporting an actual truth is usually around 50%!! Interesting concept – the Number Needed to Read (McKibbon et al., 2004) How many journal articles must you read before finding ONE quality study?  The suggested numbers may surprise you! So where do we go from here? In his paper, “Why Most Published Research Findings are False” John Ioannides suggests, Instead of chasing statistical significance, we should improve our understanding of the range of R values—the pre-study odds—where research efforts operate. Before running an experiment, investigators should consider what they believe the chances are that they are testing a true rather than a non-true relationship. Speculated high R values may sometimes then be ascertained. As described above, whenever ethically acceptable, large studies with minimal bias should be performed on research findings that are considered relatively established, to see how often they are indeed confirmed. I suspect several established “classics” will fail the test.   References * Ioannidis JP. Why most published research findings are false. PLoS Med. 2005;2(8):e124. * Mckibbon KA, Wilczynski NL, Haynes RB. What do evidence-based secondary journals tell us about the publication of clinically important articles in primary healthcare journals?. BMC Med. 2004;2:33.

Today we are lucky to have Dr. Manjari Joshi, Associate Professor of Medicine, Division of Infectious Diseases at both the University of Maryland SOM and the R Adams Cowley Shock Trauma Center. For today’s lecture, Dr. Joshi will take us through the chaotic world of antibiotic use in critical care patients. She will show us how those rushed decisions made in when we first meet our patients REALLY can determine whether a patient even survives to go home. This talk has so tips, tricks, and pearls, one viewing might not be enough! PEARLS TIP #1: Before choosing antibiotics take 3 factors into consideration: * Who is the patient you are treating (transplant, HIV, heart failure, etc..) * What environment is the patient coming from (hospital, nursing home, home…) * What organisms are possible based on local factors (exposures, recent outbreaks…) TIP #2: Always consult an antibiogram in order to choose appropriate antibiotics based on your hospital and community susceptibilities TIP #3: Leading cause of inadequate therapy is failing to consider multidrug resistant organisms (MDRO):  Tip #4: Always consider the environment you are treating: * Lung: acidic pH that can denature molecules (Aminoglycosides); surfactant that can inhibit Daptomycin * CNS, Ocular, Cardiac: low penetration, will need HIGH concentrations of antibiotics * Biofilms (heart tissue, devices): can decrease penetration, but can also decrease metabolic activity and bacterial multiplication which is vital for some abx to work Drug Factors:  * Combination therapy is for a multitude of reasons: * Initial therapy broad coverage * Synergy– when 2 drugs “augment” each other * ex: Gentamicin can be used to lower the MIC of Ampicillin in order to treat gram neg rods (GNRs) * Polymicrobial infections * Resistance prevention (ex: Tb treatment) * Bioavailbility– only 5 drugs have equal PO and IV bioavailabilities: * Linezolid, Metroniadazole, Fluoroquinolones, Trimethoprim/Sulfamethoxazole, Rifampin * PK/PD parameters– its all about the Minimal Inhibitory Concentration (MIC) * Time dependent antibiotics (β-lactams)- only effective during the time above the MIC * Want 4-5 x the MIC constantly, achieved with repeated dosing OR continuous infusions * Concentration dependent antibiotics (Aminoglycosides): the peak of the drug determines efficacy * Can do once daily dosing as even when the drug is < the MIC it is still effective (post-antibiotic activity) * Area under the curve (AUC) antibiotics (Fluoroquinolones): the size of the area under the curve determines efficacy * Clearance: renal clearance can be increased with burns, drug abuse, leukemia, need to adjust dosing! * Resistance: Increased with: 3rd generation cephalosporins, Fluoroquinolones, Carbepenems * Empiric therapy: every hour delay to initiation of abx = ↑ 8% to mortality! * Deescalation: day 3 is the time to determine if there is a need to add, subtract, or change antibiotics based on the patients recovery * Duration of therapy: newer data shows large dose of antibiotics over a shorter period of time can be better and lead to less resistance: * CAP: 3-5 days, pyelonephritis: 5-7 days, intra-abdominal infections: 4-7 days * Inflammatory markers: CRP, Procalcitonin, etc are NOT ready for mainstream use….  References & Resources *

Dr. Neal Porter is an Assistant Professor of Neurology here at the University of Maryland with a special clinical focus on neurophysiology. Over the last twenty years, Dr Porter has mastered the topic of ICU polyneuromyopathy and has used this knowledge to be one of the national experts in the field. Additionally, he consistently makes himself available here at Maryland (even WELL after hours) as the “go to” expert when it comes to evaluation and management of the weak critical ill patient. Today he is gracious enough to take us into his world and explain the simplistic and systematic way he approaches every case of weakness in the ICU. This is a talk you CANNOT miss as that next case of botulism might sneak in through your door any moment!!! Pearls Simple approach to weakness: * Time course leads to etiology * To localize/diagnose: * Focus on pattern of weakness * Associated features * Sensory abnormalities * Upper motor signs: spasticity, hyper-reflexia, upgoing toes * Lower motor signs: flaccidity, muscular atrophy, muscle fasciculations, areflexia, downgoing toes * Differentiate: * People who are weak BECAUSE they are in the ICU * People who are in the ICU BECAUSE they are weak Critical Illness Polyneuropathy/Myopathy * Disuse syndrome, severe myopathy/axonal neuropathy due to a prolonged ICU stay * Physical exam: * Muscle wasting/weakness * Areflexia or hyporeflexia * Quadraplegia/Quadraparesis * Flaccidity (leading to prolonged ventilator use) * Normal mental status * Time frame: 2+ days of ICU stay * Prevalence: 50-70% of patients * Diagnosis: clinical appearance (NO need for an EMG) * FUN FACT: Direct muscle stimulation yields no response * Treatment: Supportive measures * Prognosis: 30% recover from myopathy in 3 months * Neuropathy is more difficult- grows 1mm/day (1″ per month) * Risk factors: * Steroid use (preventable) * Paralytics/Sedation (preventable) * Prolonged Stay with ventilatory support * Sepsis * Pathophysiology of myopathy: an acquired sodium channelopathy Acute weakness PRIOR to the ICU 1) Nerve root: Guillain Barre Sydrome (GBS) * Acute areflexic paralysis (NOT ascending paralysis) * Starts with a viral prodrome → back pain (first symptom) → tingling of hands/feet → proximal>distal weakness (polyradiculopathy) * Difficulty getting out of chairs/climbing stairs * Diagnosis: demylelination nerve conduction studies (NCS) * LP shows cytoalbumination; low high protein and normal cell levels * West Nile Virus has INCREASED cells (presents similar to GBS) * Treatment: Plasma exchange (PLEX) or IVIG * Prednisone is contraindicated (small amounts leads to a worse prognosis) 2) Nerve Plexus: Parsonage-Turner Syndrome * AKA: Acute brachial neuritis * Arm pain → numbness, weakness → affects the phrenic nerve (rare cases ONLY affects the phrenic nerve) * Diagnosis: EMG * Treatment: Supportive 3) Nerves: Porphyria * Acute or recurrent paralysis similar to GBS * Presentation: abdominal pain, psychosis, weakness * Usually presents after a trigger: medication, infection, etc. * Diagnosis: NCS showing axonal loss * Screening: phorphobilinogen and delta-ALA * Treatment: supportive, avoiding offending agents 4) Neuromuscular junction: Myasthenia gravis (MG) * Acute or subacute diplopia, dysphagia,

Dr. Anthony Harris is a Professor of Medicine at the University of Maryland and an expert in infection control as well as epidemiology.  He recently published a paper in JAMA on the effects of universal glove and gown use on antibiotic-resistant bacteria acquisition and colonization in the ICU with some interesting results… We were fortunate enough to have Dr. Harris come and discuss his thoughts about infection control in the ICU as well as some simple ways we can help prevent our sickest patients from getting even sicker.  Plus… he’s Canadian – so you know this has to be good. Pearls The hospital is filled with bacteria – the ones we worry about most – ESKAPE bugs * Enterococcus faecium (VRE) * Staph aureus (MRSA) * Klebsiella pneumoniae (CRE) * Acinetobacter baumannii * Pseudomonas aeruginosa * Enterobacter spp. Unfortunately, more than 50% of surveillance culture colonization and acquisition of nosocomial bacteria is transferred by the healthcare worker!! How important are gloves and gowns? Major Concepts in Infection Control * Hand hygiene, hand hygiene, hand hygiene * Active surveillance: Up to 90% of colonizations will be miss if you only wait for clinically (+) cultures, however, colonized patients transmit bacteria just as easy as those who are clinically infected! * How to perform surveillance cultures: * MRSA: Nares or wound swabs * VRE: Perianal swabs * ESBL: Perianal swabs * CRE: Perianal, urine swabs * MDR Acinetobacter ??? * Environmental cleaning:  If you culture objects in a room after a surveillance (+) patient is moved (and the room is cleaned), up to 20-30% of the entire room is actually clean. * Antibiotic stewardship * Decolonization: Promising data that suggests this could be affective – at least for MRSA. * Universal gowning & gloving * Improves hand hygiene on exit * Found to have a large decrease in MRSA acquisition (by 40%!!) * No effect on VRE acquisition (unclear why) * Trend toward decreased adverse events – but no difference in CLABSI, CAUTI, VAP rates * Get unnecessary catheters out early   References & Resources * Harris AD, Pineles L, Belton B, et al. Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial. JAMA. 2013;310(15):1571-80. * Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-65.

Today we are fortunate to have Avelino Verceles, Associate Professor of Critical Care and Pulmonary Medicine here at the University of Maryland as well as acting director and architect of one of the most successful ventilator weaning programs in the Northeast. Over the next hour, Dr. Verceles will explore the devastating complications suffered by the “survivors of critical illness” and explain the way rehab can save more then just muscle mass….. Pearls:  Background * 90% of patients who suffer an acute critical illness will quickly recover or die * 10% of patients will be classified as “survivors of critical illness” * Prolonged mechanical ventilation, tracheostomy, deconditioned, multiple comorbidities * Consume 40% of ALL ICU resources during their ACUTE stay (or $20 billion!!) * 40% of all ICU admissions are mechanically ventilated for a mean time of 2-4 days * 5-20% will remain intubated >7 days * At 21 days the patient is qualified as “chronically critical ill” * 75% of the chronically critical ill are over the age of 50yo * FACT: 1/2 of all patients admitted to the ICU >65yo will eventually be qualified as chronically critical ill * Complications of prolonged mechanical ventilation: * Delerium, PTSD, ↓ cognitive function, ↓ quality of life * Malnutrition: under- or over-feeding * Sarcopenia, muscle atrophy, deconditioning, loss of function → decreased mobility * Critical illness neuromyopathy * 50% of patients admitted with sepsis and/or multiorgan failure will suffer severe myopathy * 90% of patients will have persistent abnormalities at 5 years * 50% of ICU survivors have severe difficulties with ADLs at 1 yr Weaning >50% of chronically critically ill patients can be weaned by 1 yr of discharge * Ventilator associated pneumonia (VAP) effects 40% of pts ventilated >7 day * There is a cumulative 1% risk of developing a VAP every day the patient is ventilated * #1 way to wean off the vent is via respiratory therapist driven protocols (30-53% weaning rate!) * Rapid Shallow Breathing Index (RSBI): RR/VT * Spontaneous Breathing Trial (SBT) * Out of bed to chair (OOBTC) * Pulmonary toileting, Percussion therapy * When to start weaning: * Acute problem has resolved * Hemodynamically stabilized * Appropriate mental status * Airway intact * SBT is tolerated * Process of performing a SBT: * Short (30 mins) vs long (120 mins): equal extubation, intubation, and mortality rates * Trach collar trials have better outcomes than decremental pressure support trials (Jubran A. JAMA 2013) Nutrition * 43% of critically ill are malnourished (under- or overfed) leading to poor outcomes * ↑ proteolysis, ↑ cellular use of protein, ↓ creation of albumin (all efforts switched to creating acute phase reactants) * ↑ risk of infections, ↑ ICU LOS, ↑ mortality, ↓ ventialtor free days * Kwashiorkor malnutrtion: ↓ lean tissue mass, anasarca, hypo-oncotic state * Refeeding syndrome: reintroduce a large nutritional load → insulin surge → electrolyte abnormalities (↓PO4, ↓Mg,

Dr Henry Masur is a clinical expert in HIV from the National Institute of Health (NIH) who has published over > 300 peer reviewed publications related to infections and HIV.  We were tremendously lucky to have hime come up to Baltimore and give a really nice review on the history of HIV as well as some major pearls and pitfalls to consider the next time your managing a patient with HIV patient in your ICU.  You think you may know how to manage the sick patient with the classic opportunistic infection – but what about the trauma patient with HIV?  How about that HIV patient who just had an MI?  You can really make some big mistakes if you go at it alone. * We may not be making as much progress as we think in HIV care * HOPS Study – while optimistic, is based on a sample of patients who are compliant with out-patient care. * NHDS – based on discharge summaries, shows we may not be doing that well with treating HIV and preventing OI’s. * For any HIV patient in the ICU – it should automatically trigger you to give your friendly Infectious Disease consultant a call.  Medications are complex, have lots of interactions, and shouldn’t be managed alone. * Pearl:  When do opportunistic infections occur? The CD4 cut off may not be what you were actually taught!! * There is no absolute cutoff, they are +/- * Many of the “cutoffs” were arbitrarily made into round numbers so that it’s easy for you to remember! * HIV issues to be aware of: * Absorption issues: Resistance to subtherapeutic levels (nearly all meds are oral) of HIV meds can happen within DAYS.  Once a resistance is established, they will have forever lost the ability to take that antiretroviral ever again. * Toxicities: * Abacavir: Distributive shock (Sepsis mimic), desquamating rash, hypersensitivity syndrome. * Dapsone: Methemoglobinemia * Fluconazole, bactrim, INH, rifampin: hepatitis * Drug Interactions:  Often interact with many drugs used in the ICU * Ritonavir, Rifampin – lots of interractions * Immune Reconstitution Inflammatory Syndrome (IRIS) * Important to ask your HIV patient when they started their anti-retroviral therapy (ARVs) – classic time line for IRIS is days to weeks. * HIV & Pneumonia – Pneumococcus, Hemophilus, PCP, Tuberculosis, & Atypicals/Viral infections are the most common causes. Don’t for get about S. Aureus either! * Refractory PCP: Clindaprimaquine is just as good as IV Pentamadine.  Atovaquone is a BAD CHOICE due to the fact that it’s an oral drug and has the potential for erratic absorption and subtherapeutic levels. * HIV + CNS Mass lesions:  CD4 < 100 – think Toxoplasma or Lymphoma.  If the CD4 > 100, it’s not Toxo, think lympoma, Tb, or something else. References * Fauci AS, Folkers GK. Toward an AIDS-free generation. JAMA. 2012;308(4):343-4. * Steinbrook R. HIV/AIDS in 1990 and 2012: from San Francisco to Washington, DC. JAMA. 2012;308(4):345-6.

Today we are honored and privileged to have one of the premier minds in the field of critical care epidemiology, Dr. Burton Lee. In addition to his role as program director of the Pulmonary Critical Care & Emergency Medicine Critical Care Fellowship at the MedStar Washington Hospital Center, Dr. Lee spends a significant amount of time transforming the most complex statistical analysis techniques into such simplistic terms that even a novice can fully comprehend. Today we learn the tips and tricks to tackle numeracy and the α-error, 2 topics that you THINK you know, but do you really get it?!? Pearls:  * Numeracy: mathematical competence, ie: applying simple concepts of mathematics to reason * Apophenia: seeing patterns in randomness/meaningless data (example: pictures in the clouds) * Type I error or α-error: conclude a “pattern” or “result” when data is truly random  * Type II error or β-error: incorrectly conclude no pattern exists * In order to be an astute reader of the medical literature you must understand the pitfalls of four commonly used statistical methods: * Multiple Testing: with multiple testing of the same concept, eventually you will get a positive study (by chance alone) * * Will see an eventual elimination of α-error * ex: Wenzel. NEJM 2004; 350:105-13. * Outcome changes: fitting the outcome of a study to a more publishable, “positive outcome” * Lessens adherence to α-error and hurts the overall power of the study * JAMA 2009;302:977-84 * Can be remedied with preregistered outcomes: http://clinicaltrials.gov/ * Publication bias: publication of only studies that support a desired outcome * Turner. NEJM 2008;358:252-60 * The only solution is to report ALL clinical trials, again reliance on http://clinicaltrials.gov * Subgroup analysis: making conclusions by post-hoc analysis of randomly chosen subgroups * ISIS-2. Lancet 1988;ii:349-60 * Remedied with pre-specification of subgroups prior to experimentation (not meant to replace hypothesis generation) * Criticize existing subgroup analysis by 2 methods: * Draw a vertical line through the “all” group, if it can hit all the subgroups, there is no significance! Just check the p-value of heterogeneity (interaction) De Backer. NEJM 2010;362:779-789 References * Mathieu S, Boutron I, Moher D, Altman DG, Ravaud P. Comparison of registered and published primary outcomes in randomized controlled trials. JAMA. 2009 Sep 2;302(9):977-84. * Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008 Jan 17;358(3):252-60. * Begley CG, Ellis LM. Drug development: Raise standards for preclinical cancer resea...

Today we are pleased to welcome Dr. Majid Afshar, one of the newest members of the Division of Pulmonary & Critical Care Medicine at the University of Maryland. Today he was willing to share his tips and tricks to sorting out the handful of good research among the thousands of paper released every year. In the next 45 minutes he will take you from entry level novice to epidemiology expert! Pearls Internal Validity  * Error Types: * Random Error: depends on chance alone (ex: flipping 10 coins) * Decreases as sample size increases * Systemic Error or Bias * Survival Bias/Incidence Prevalence Bias: selective survival among the prevalent cases * Loss to Follow-up Bias * Publication Bias: only publish positive studies * Information Bias * Misclassification Bias: ex: Recall Bias, Observer Bias, Interviewer Bias, Dilution Bias  * Lead Time Bias: early diagnosis falsely appears to prolong survival * Confounding * An apparent association between disease and exposure caused by a third factor not taken into consideration * Can be avoided with a RCT or with Matching External Validity  * Measures of Effect * Control event rate (CER) = c/c+d * Experimental event rate (EER) = a/a+b * Relative Risk (RR) = EER/CER=(a/a+b)/(c/c+d) * Relative Risk Reduction (RRR) = CER-EER/CER * commonest reported measure of dichotomous treatment effect * Absolute Risk Reduction (ARR) = CER-EER * Number Needed to Treat (NNT) = 1/ARR * Odds Ratio (OR) = a*d/c*b * OR estimates the RR ONLY if disease is rare * Composite Outcome * Combine a number of individual outcomes (such as types of morbidity) * Used when no obvious choice of primary endpoint * Allows for a smaller sample size and/or a shorter follow-up * However: difficult to use and interpret, leading to errors in sample size estimation, possible contradictory trial results, and difficulty in interpreting findings. * Subgroup Analysis * Evaluate treatment effects and/or specific outcomes in subgroups of patients * Often difficult to interpret, as subgroups are often only identified after the fact (not a priori) References * Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009;374:1351-63. * Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002;347:1143-1150. * Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988 Aug 13;2(8607):349-60.

Dr. Carl Shanholtz was the man of the hour at the University of Maryland Multidisciplinary CC Conference this week, here to discuss his “Plan B – Z” for patients with refractory hypoxia despite your best efforts.  Dr. Shanholtz is one of the few PI’s of the ARDSnet collaboration and shares an amazing evidence based walkthrough of the different salvage therapies we have available to us when you must throw the proverbial kitchen sink at your dying patient.  What do you have in your back pocket? Pearls * General Housekeeping * Beware of studies where outcomes are compared against historical controls – standard of care and practices change, which will bias the data. * We all know to keep the plateau pressure < 30 mmHg, but there doesn’t appear to be a safe Pplat that you can ignore low-tidal volumes (Hager et al., 2005). * For patients with reasonable hemodynamics and ARDS, practicing a fluid restrictive strategy appears to improve outcomes. * Now this is a big one – remember, fluids are drugs! * Keep a close and constant eye on the cumulative I/O balance sheet.  You’ll be surprised at how positive your patients actually are if you don’t keep track! * It has been suggested that up to 10% (over 5,000) of the overall mortality from ARDS is a direct result of iatragenic hypervolemia! * Proning * Concept: Reducing the amount of atelectasis and alveolar edema at the bases as well as the posterior segments due to the weight of the patient’s heart, body tissue, gravity, etc. while lying supine for an extended period of time. * No statistical benefit demonstrated for all-comers with ALI/ARDS, however… * For patients with moderate to severe ARDS (P/F < 200) there does appear to be significant benefit to proning. * Guerin et al., 2013 – for patients with severe ARDS found a reduction in 28 & 90 day mortality by 50%. * Neuromuscular blockade * Concept: Reducing ventilator dyssynchrony will reduce biotrauma of lungs and minimize iatragenic inflammation/edema in lungs. * Technique: Cistatracurium infusion x 48 hours (Papazian et al., 2010) * May have some outcome benefit. * Inhaled vasodilators * Concept:  By using an inhaled vasodilator, you can improve V/Q mismatch by preferentially dilating pulmonary vasculature that’s perfusing unaffected lung – unlike an intravenous Rx that theoretically would just increase your shunt fraction. * Multiple studies on iNO, but does not appear to have a significant impact on outcomes for hypoxemic respiratory failure, specifically in ARDS (Adhikari et al,. 2007). * Extracorporeal Life Support (ECLS/ECMO) * Historically, ECLS technology was pretty poor – however, improved circuit technology has increased the availability, reduced blood trauma, and increased the length of support that can be provided. * The CESAR trial (Peek et al., 2007) is intriguing, however the significant benefit in death & disability (composite endpoint, not a primary endpoint) in the ARDS group managed with ECMO, and…. there was an asterisk. * (*) The treatment arm may have not actually received treatment (i.e. ECMO) – 1/4 of these patients received “standard treatment” but were merely transferred to an ECMO capable center. * Other confounders (treatment center variation, low tidal volume ventilation strategy,

Today we are fortunate to have Dr. Ashutosh (Ash) Sachdeva, director of the University of Maryland Interventional Pulmonology Service and all around bronchoscopic wizard, to speak to us on his passion: how to save a failing airway. Over the next 60 minutes, Dr. Sachdeva will walk you through three procedures he feels that everyone staffing an ICU needs to know how to perform in their sleep. He may even toss in a few bronchoscopic secrets along the way. 1) Cricothyroidotomy * Simple technique in the right hands; however: need prior experience with technique before grabbing the scalpel (often takes 5 simulated attempts to be comfortable) * Indications: can’t intubate/can’t ventilate (for a multitude of reasons), loss of upper airway landmarks (edema, facial/nasal injuries) * Contraindications: overlying infection, tracheal injury, obscuring of landmarks (mass), age <12 * Adverse effects (based on prior studies): voice change (50%), tracheal stenosis (2%) * Cheap kit: scalpel, bougie, 4-6 sz ETT and steady hands, though Seldinger-based kits are available 2) Percutaneous tracheostomy * Advantages: short procedure, smaller incision needed, done at bedside (though OR can be used), lower VAP and lower LOS * Disadvantages: requires bronchoscopic guidance (can injure bronchoscope), need advanced airway training * Seldinger kits are available for ease of placement, though there is still need to visualize with bronchoscopy throughout the entire procedure (need 2 trained operators) * Complications: puncture of posterior wall (by far most worrisome) & occlusion of trach with posterior wall tissue (due to inflammatory state) 3) Hemoptysis  * Actual definition varies: from 200 cc/hr of bleeding (healthy lung) to as low as 50 cc/hr (chronic respiratory failure) OR >2 episodes of moderate hemoptysis (~30cc) in 24 hours * Cause: 90% from bronchial circulation (though non-bronchial sources can be more severe) * CT scan with angio is gold standard; CXR will be diagnostic only 50% of the time * Bronchoscopy: can help localize bleed and tamponade (bronchial blocker) to salvage healthy lung **Special Note: Tracheo-innominate artery fistula– due high riding innominate or low riding trach (below 4th tracheal ring– most common cause); appears by week 3-4, often preceded by sentinel bleed!** References * Ernst A, Feller-Kopman D, Becker HD, and Mehta AC “Central Airway Obstruction”, American Journal of Respiratory and Critical Care Medicine. 2004;169(12):1278-1297. * Theron J, Diacon AH, and Bolliger CT. Chapter 7. Management of massive haemoptysis. European Respiratory Monograph 36: Respiratory Emergencies. 2006;36:95-107. * De Leyn P, Bedert L, Delcroix M, Depuydt P, Lauwers G, Sokolov Y, Van Meerhaeghe A, and Van Schil P. Tracheotomy: clinical review and guidelines. Eur J Cardiothorac Surg. 2007;32:412-421. * Sachdeva A, Shepherd RW, Lee HJ. Thoracentesis and thoracic ultrasound: state of the art in 2013. Clin Chest Med. 2013 Mar;34(1):1-9.

This week, Dr. Bryan Hayes – Clinical Pharmacologist and expert in Toxicology gives an amazing talk highlighting 10 of his top tips for antimicrobial use in the emergency department & for the critically ill patient.  This is probably one of the most clinically useful lectures I’ve listened to in a long time.  Bryan has actually started his own campaign to make sure we are all using Vanc right in 2014 – he even made it a New Years Resolution of his own (Check out his post on Academic Life in EM) Pearls * How to correctly give a dose of vancomycin * Dose: 15-20 mg/kg every 8-12 hours in patients with normal renal function, MAX: 2 grams * Consider an even higher loading dose In seriously ill patients (e.g. sepsis, meningitis, infective endocarditis) with suspected MRSA infection: 25-30 mg/kg — again, MAX 2 grams (ISDA recommendation). * Weight based dosing by using actual body weight * In adults, we round to the nearest 250 mg increment (to help out your friendly pharmacist) * In the critically ill obese patient, aminoglycosides should be dosed by adjusted body-weight * ABW = Ideal BW + 0.4*(Actual BW – Ideal BW) * A Penicillin allergy is NOT a contraindication to cephalosporin use! * 3rd, 4th, & 5th Generation cephalosporins can be safely given to PCN allergic patients. * Avoid keflex, cefaclor, cefadroxil, cefprozil as their beta lactam side chain is similar to PCN. * Carbapenems are also safe in PCN allergic patients * HCAP “double coverage” should include only 1 beta-lactam antimicrobial, the 2nd agent should have a different mechanism of action (i.e. fluoroquinolone, etc.) * Don’t forget the atypical coverage in HCAP patients!  Send the urine legionella antigen. * CAP patients admitted to the ICU should not be treated with a fluoroquinolone alone.  Add the beta-lactam. Thanks Bryan – we’ll make sure to get it right in 2014. References * Ryback M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm2009;66(1):82-98. * Rosini JM, et al. Prescribing habits of vancomycin in the emergency department: are we dosing appropriately? J Emerg Med 2013;44(5):979-84. * Liu C, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clin Infect Dis 2011;52(3):e18-55. * Fuller BM, et al. Emergency department vancomycin use: dosing practices and associated outcomes. J Emerg Med 2013;44(5):910-8. * Frankel KC, et al. Computerized provider order entry improves compliance of vancomycin dosing guidelines in the emergency department. Am J Emerg Med 2013;31(12):1715-6. * Campagna JD, Bond MC, Schabelman E, Hayes BD. The use of cephalosporins in penicillin-allergic patients: a literature review. J Emerg Med. 2012;42(5):612-20.