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Bacterial Meningitis – Summary

Introduction:

  • inflammation of the leptomeninges (arachnoid mater + CSF)
  • among 10 most common infectious causes of death (135,000 deaths/world/year)

Epidemiology

  • Community or Healthcare associated
    • Community: Strep pneumo, Neisseria meningitidis, Listeria monocytogenes (pt over 50-60 yr old or cell-mediated immunity)
    • Healthcare-associated: generally staphylococci or anaerobic gram-negative
      • Risks: neurosurgery, VP drain placement, trauma w/ leakage of CSF

Clinical Features — pts often present soon after symptom onset

  • Classic triad: fever + nuchal rigidity + AMS, though most pts do not have all 3
    • Review of 279 episodes of community acquired meningitis
      • Most common is fever with temp > 38C (95% at presentation, another 4% w/n 24h)
      • Nuchal rigidity (88% on initial examination)
      • AMS (78%, confusion + lethargy most common)
    • Three other large series showed:
      • Fever (77-85%), neck stiffness (83-94%), headache (79-94%), AMS (83%)
    • 2004 Review of 696 cases of community-acquired bacterial meningitis
      • Classic triad in only 44% patients (fever, neck stiffness, AMS)
        • More common in pneumococcal than meningococcal meningitis (58% vs 27%)
      • 95% had 2 out of 4: fever, neck stiffness, AMS, HA, 99-100% with at least one sign
        • Therefore, absence of all findings essentially excludes the diagnosis of bacterial meningitis
  • Kernig’s & Brudzinski signs
    • Brudzinski: spontaneous flexion of hips w/ passive neck flexion
    • Kernig: inability or reluctance to allow full extension of knee when hip is flexed to 90 degrees
    • Prospective study of 297 patients in 2002 – meningitis defined as > 6 WBCs in CSF
      • Low sensitivity (5% each kernig/brudz and 30% nuchal rigidity), specificity 95% for kernig/brudz and 68% for nuchal rigidity

Course

  • Determinants of pace are related to hot and microbial virulence factors
    • If late to treatment, course is almost uniformly fatal

Assessment of Risk

  • Prognostic model of 176 adults and another cohort of 93 patients
    • 9% with neurologic deficit at discharge
    • Baseline clinical features (hypotension, AMS, sz) independently assoc w/ adverse outcome
      • Low risk (no clinical risk factors) – 9% adverse outcome
      • Intermediate (1 clinical risk factor) – 33% adverse outcome
      • High (2-3 risk factors) – 56% adverse outcome

Laboratory Features – often unrevealing

  • CBC: generally elevated WBC with left shift, though severe infxn may present w/ leukopenia
    • Plt: may be reduced
    • Leukopenia + thrombocytopenia associated with poorer outcomes
  • Coags: may be consistent with DIC
  • BMP: AGMA or hyponatremia
  • Blood Cultures: often positive and useful if CSF cannot be obtained p/t abx
    • 50-90% pts w/ bacterial meningitis will have (+) cultures
  • LP: crucial for diagnosis
    • May delay for CT scan in order to r/o mass lesion or increased ICP — would lead to herniation w/ removal of large amount of CSF
      • However, screening CT not necessary for majority of patients
        • Prospective Study of 301 w/ suspected meningitis: 235 underwent CT before LP —24% had abn finding, but only 5% had mass effect
          • Risk of abn finding often predicted by suspicious hx (ex. impaired cellular immunity, hx prior CNS disease or seizure in past week) as well has PE (reduced LOC, focal motor weakness or cranial abn)
            • Among 96 pts with none of these features, only 3 had abn CT, 0 w/ herniation
        • Compared w/ pts who did not have CT before LP, those who did had average 2 hours delay in dx and 1 hour delay in tx
    • ISDA Guidelines of CT before LP — get CT if:
      • Immunocompromised state (HIV, immunosuppressive tx, solid organ or hematopoietic stem cell txp)
      • Hx CNS disease (mass lesion, stroke, focal infection)
      • New onset seizure
      • Papilledema
      • Abn LOC
      • Focal neurologic deficit
    • Clinical signs of impending herniation: deteriorating LOC (GCS < 11), brainstem signs (ie. pupillary changes, posturing, irregular respirations), very recent seizure
      • suggest delaying LP
    • If Delayed LP
      • 1) Obtain blood cx immediately
      • 2) Begin empiric abx + dexamethasone (0.15 mg/kg IV) s/p blood cultures
        • Important to begin dexamethasone BEFORE or AT SAME TIME as ABX, not after
        • Pathogen may still be cultured from CSF in most patients up to several hours after administration of abx
      • 3) Obtain LP as soon as possible after imaging study
    • Opening Pressure — typically elevated in bacterial meningitis
      • Series of 301 adults: mean opening pressure 350 mmH2O (normal up to 200)

CSF Analysis

  • What to get
    • Cell count + differential, glucose, protein, gram stain + culture
  • Clinical findings will suggest meningitis, the CSF will differentiate the type
    • Normal CSF: < 50mg/dL protein, CSF to serum glucose ratio > 0.6, < 5 WBCs, lactate concentration < 3.5 mEq/L
  • Bacterial Meningitis
    • WBC: 1000 – 5000/microliter, Neutrophils > 80%, Protein > 200 mg/dL, glucose < 40 mg/dL
      • CSF:serum glucose </= 0.4)
    • Observational study: 99% probability of bacterial meningitis if one of following present:
      • CSF glucose < 34 mg/dL, Protein > 220 mg/dL, WBC > 2000, neutrophil count > 1180
    • Lactate: 2 meta-analyses including 25 & 31 studies
      • determined that CSF lactate superior to WBC, glucose and protein in differentiating bacterial from aseptic meningitis — lower sensitivity if abx p/t LP & falsely elevated if concurrent CNS disease present
    • Pleocytosis: false-positive elevate of WBC found in few instances
      • traumatic LP, intracerebral or SAH (both RBC and WBC introduced to arachnoid space), generalized seizures (temporary pleocytosis)
    • Gram Stain
      • G (+) diplococci suggests pneumococcal infection
      • G (-) diplococci suggests meningococcal infection
      • Small pleomorphic G (-) coccobacilli suggests Haemophilus influenzae infection
      • G (+) rods + coccobacilli suggets listeria
      • Reported sensitivity of gram stain 60-90%, but specificity approaches 100%
        • Study of 696 patients w/ community-acquired bacterial meningitis
          • Sensitivity of gram stain 80%, specificity 97%
      • Gram stain may be positive in 10-15% patients who have a negative culture
    • Limited Utility in repeat LP to assess response to therapy
      • Repeat if: 1) no evidence of improvement by 48 hours 2) 2-3 days after initiation of tx due to microorganisms resistant to standard agents and are not responding as expected or for infection caused by gram-negative bacillus 3) persistent fever for more than 8 days w/o other explanation

Treatment

Effects of Delay to Treatment

  • Retrospective study of 269 adults with bacterial meningitis
    • 3 baseline prognostic markers (HoTN, AMS, Sz) predictive of adverse outcome (in-hospital mortality or neuro deficit at discharge)
      • Delay to tx in ER (median time 4 hours) associated with worsening of these markers in 15% patients
  • Prospective study of 156 patients w/ pneumococcal meningitis
    • Delay more than 3 hours after hospital admission = independent risk for mortality (odds ratio 14.1: 95% CI 3.9 – 50.9)
  • Retrospective cohort of 286 patients with community-acquired bacterial meningitis
    • Early/adequate ABX in r/t onset of overt s/s —> favorable outcome (mild or no disability) (OR 11.2, 95% CI 4.4 – 32.6)

Why would there be a delay?

  • Atypical presentation = absence of fever on presentation, lack of headache/neck stiffness
  • Imaging delay to exclude presence of mass lesion or risks for cerebral herniation
    • If going to delay LP, MUST begin ABX/Steroids while obtaining blood cultures

Antibiotics

  • Three general requirements
    • 1) bactericidal drugs effective against organism 2) drugs entering CSF 3) structuring regimen to optimize bactericidal efficacy
    • Bactericidal drugs: CSF = space of impaired humoral immunity
    • CSF entry: normal BBB = blockage of beta-lactams (ex. PCN), if meningeal inflammation —> separation of intercellular tight junctions but decr. permeability as inflammation decreases blocking antimicrobial entry
      • Therefore, maximal parenteral doses must be continued throughout course to maintain adequate CSF concentration
    • Pharmacodynamics: bactericidal activity depends on time above minimal inhibitory concentration for time-dependent drugs (ex. beta-lactams, vancomycin)
      • Concentration-dependent antimicrobials (ex. aminoglycosides), killing of bacteria occurs over wide range of antimicrobial concentrations w/ prolonged recovery period
  • Empiric Therapy
    • Causative Organisms — CDC study of 1083 cases meningitis 2003 – 2007
      • S. pneumo 71%, N. meningitidis 12%, Group B Strep 7%, H influenzae 6%, Listeria monocytogenes 4%
        • Incidence of Listeria increases with age — empirically tx if age > 50 (ampicillin)
    • Regimens
      • 1) Third generation cephalosporins (ex. cefotaxime + ceftriaxone)
        • Consistent CSF penetration + potent activity against major bacterial pathogens (exception being L. monocytogenes & some PCN-resistant S. pneumo strains)
      • 2) Vancomycin
        • Empiric tx for pcn-resistant strains until cultures & susceptibilities return
      • Others:
        • Ceftazidime (3rd generation ceph w/ broad activity against gram-negative bacteria including Pseudomonas
          • Much less active against PCN-resistant pneumococci than cefotaxime & ceftriaxone
        • 4th Generation cephs including cefepime — safe & equivalent to cefotaxime for bacterial meningitis in infants and children
    • No known Immune Deficiency
      • Bugs: S. pneumo, N. meningitidis, less often H. flu & GBS — up to 60 yo
        • 1) Ceftriaxone 2g IV q 12h OR Cefotaxime 2g IV q4-6h, PLUS
        • 2) Vancomycin 15-20 mg/kg IV q 8-12h (not to exceed 2 g per dose or total daily of 60 mg/kg, IF
        • 3) Adults > 50 also get Ampicillin 2 g IV q 4h
    • Impaired Cellular Immunity — ex. lymphoma, cytotoxic chemotx, high-dose glucocorticoids
      • Bugs: Listeria monocytogenes, gram-negative bacilli (including Pseudomonas), S. pneumo
        • 1) Vancomycin – 15-20 mg/kg IV q 8-12h — not to exceed 2 g per dose, PLUS
        • 2) Ampicillin – 2 g IV q 4h, PLUS EITHER
        • 3) Cefepime 2 g IV q 8h OR Meropenem 2 g IV q 8h
    • Healthcare-associated Infection (i.e. s/p trauma, surgery, pts w/ VP drains)
      • Bugs: Gram-positive & gram-negative (i.e. Kleb, Pseudo)
        • 1) Vancomycin (dosing as above), PLUS
        • 2) Ceftazidime 2 g IV q 8h OR Cefepime 2 g IV q8h OR Meropenem 2g IV q8h
      • Question of withdrawing abx if CSF culture negative & suggest aseptic picture vs bacterial s/p neurosurgery
        • Consensus is to continue abx in all patients w/ clinical & lab features suggesting meningitis and discontinue 48-72 hours s/p CSF culture negative
    • Beta-Lactam Allergy
      • 1) Vancomycin (dosing as above), PLUS
      • 2) Moxifloxacin 400 mg IV qD, PLUS
      • 3) TMP-SMX 5 mg/kg IV q6-12h if age > 50 or listeria otherwise suspected

Adjunctive Dexamethasone

  • Early IV administration of glucocorticoids evaluated as adjunctive tx in attempt to diminish hearing loss, other neuro complications and mortality
  • Main indication: pneumococcal meningitis
    • Since etiology often not known at time of presentation, administer prophylactically
  • Rationale provided by animal studies — decreased hearing loss temporarily associated with severe inflammatory changes induced by meningitis — decreased w/ dexamethasone
  • Regimen: 0.15 mg/kg q6h x 4 days
    • Consider adding rifampin to abx if pneumococcal meningitis and receiving dexamethasone
      • if susceptibility studies show intermediate susceptibility (MIC >/= 2) to ceftriaxone and cefotaxime

Prognosis

  • Mortality: increases linearly with age
    • 16.4% mortality in adults (8.9% 18-34 yo vs 22.7 in adults > 65)
    • Higher rates of mortality with healthcare-associated infection vs. community acquired (35 vs 25%), higher with infection due to S. pneumo & L. monocytogenes vs N. meningitidis (28 & 32% vs 10%)
  • Neurologic
    • 28% community acquired patients in study of 493 episodes resulted in neuro sequelae
      • Includes: impaired mental status, increased ICP & cerebral edema, seizures, focal neuro deficits, cerebrovascular abnormalities, sensorineural hearing loss, intellectual impairment

Source: Bacterial Meningitis – UptoDate

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Acute Pancreatitis – NEJM Review notes

Causes

  • Gallstones (40%)
    • Migrating gallstones -> transient obstruction
    • No convincing data showing that Sphincter of Oddi or Pancreas Divisum play a role in AP
  • ETOH (30%)
    • 4-5 drinks per day x 2-5 years — overall lifetime risk 2-5%
      • Type of ETOH consumed does not affect risk
      • Binge drinking in absence of chronic, heavy ETOH use does not precipitate AP
    • Typically flares superimposed on chronic pancreatitis
    • Mechanism: direct toxicity and immunologic mechanisms
  • Drugs (< 5%)
    • Hundreds implicated — notables are Azathioprine, 6-MP, didanosine, valproic acid, ACE-i, mesalamine
    • “Exceedingly difficult to determine whether drug is responsible”
      • Evidence of drug allergy (ex. rash) in rare cases
  • Genetics
    • Cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin C, calcium-sensing receptor, claudin-2
      • claudin-2 mutation interacts synergistically with ETOH
  • Hypertriglyceridemia (2-5%)
    • Fasting triglycerides > 1000 mg/dl
  • ERCP (5-10%)
  • Autoimmune (< 1%)
    • Type 1: obstructive jaundice, elevated serum IgG4 levels, response to glucocorticoids
      • Systemic disease involving pancreas, salivary glands, kidneys
    • Type 2: possible presentation as AP, occurrence in younger patients, no IgG4 elevation, response to glucocorticoids
      • Only pancreas is affected
  • Associated Conditions: Smoking, Obesity, DM (increases risk of AP by factor of 2-3)

Epidemiology

  • Admissions increased by 20% over past 10 years – tracks with obesity epidemic and increasing rate of gallstones
  • Mortality, decreased over time to 2% cases
    • 80% cases are mild, self-limited disease
    • Risks for mortality include: 1) elderly 2) numerous/severe coexisting conditions (i.e. obesity) 3) hospital-acquired infection 4) severe acute pancreatitis (multi-organ failure)

Diagnosis and Classification

  • 2 of 3 diagnostic criteria must be met:
    • 1) Abdominal pain consistent with AP
    • 2) Serum Lipase or Amylase levels at least 3 x ULN
    • 3) Findings of AP on cross-sectional imaging (CT or MRI)
  • Moderately Severe and Severe AP defined by presence of systemic complications, local complications or both
    • Systemic Complications: failure of organ system, exacerbation of preexisting disorder (i.e. COPD, heart failure, chronic liver disease)
    • Local Complications: peripancreatic fluid collections or pseudocysts, pancreatic/peripancreatic necrosis (either sterile or infected)
    • Persistent failure of organ system (i.e. lasting > 48 hours) is the prime determinant of poor outcome — mortality approaches 30% in these patients

Predicting Severity

  • Clinical factors increasing risk of complications or death:
    • 1) Advanced age (> 60 years old)
    • 2) numerous & severe coexisting conditions (score >/= 2 on Charlson comorbidity index)
    • 3) Obesity (BMI >/= 30)
    • 4) Long-term, heavy ETOH use (4-5 drinks/day)
  • Laboratory Measurements
    • Primarily act as measurements of volume depletion due to third space losses or markers of inflammation
    • Most useful predictors:
      • 1) Elevated BUN + Creatinine
      • 2) Elevated hematocrit
        • Especially if these do not return to normal after fluid resuscitation
    • The DEGREE of serum lipase or amylase level has NO PROGNOSTIC VALUE
  • Imaging
    • CT evidence of severe AP lags behind clinical findings
      • Early CT studies may underestimate severity
  • Scoring Systems
    • Include: APACHE II, APACHE-O (obesity), Glasgow, HAPS, PANC 3
      • High false positive rates
      • Generally cumbersome and not routinely used
  • SIRS
    • SIRS persisting longer than 48 hours is indicative of poor prognosis
    • During first 48-72 hours, rising Hct or BUN or Cr levels, persistent SIRS after adequate fluid resus or presence of pancreatic or peripancreatic necrosis on imaging constitutes evidence of evolving severe pancreatitis

Management

  • Fluid Resuscitation
    • Aggressive hydration in first 24 hours reduces morbidity and mortality
      • 1) Balanced crystalloid solution at 200 – 500 cc/hour, or 5-10 ml/kg/hr
        • Comes out to 2500-4000 cc/24 hr in first 24 hours
        • One trial indicates LR superior to NSS for reducing inflammatory markers
        • Tailor fluid therapy to degree of IV volume depletion and cardiopulmonary reserve that is available to handle the fluid and prevent fluid overload
        • RCTs needed to assess type of fluid, rate and goals of therapy – most recs are made on expert opinion alone without RCTs to back them up
  • Feeding
    • Mild AP: no need to hold feeds until resolution of pain or normalization of enzyme levels
      • Low-fat or solid diet preferred over clear-liquid diet
    • Artificial, enteral feedings predicted by day 5 based on symptoms
      • Nasogastric or nasoduodenal feedings are clinically equivalent to nasojejunal feeds
    • Early initiation of NG feeding (w/n 24h) is NOT SUPERIOR to waiting 72h until initiation – even with patients predicted to have severe or necrotizing pancreatitis
      • Don’t bother with TPN
  • Antibiotics
    • No benefit of prophylactic antibiotics – not recommended for any type of AP unless infection is suspected for has been confirmed
  • Endoscopic Therapy
    • ERCP – indicated if evidence of cholangitis superimposed on gallstone pancreatitis
      • also reasonable if choledocholithiasis suspected or findings of persistent bile duct stone (ex. jaundice, progressive rise in liver enzymes or persistently dilated bile duct)
        • ERCP not beneficial in absence of these findings
  • Treatment of Fluid Collections and Necrosis
    • Acute fluid collections do NOT require therapy
      • Symptomatic pseudocysts managed with endoscopic techniques
    • Necrotizing Pancreatitis – initially mix of semisolid & solid tissue
      • Becomes more liquid and encapsulated after 4 weeks
      • Sterile necrosis does not require therapy unless obstructing nearby viscus (ex. duodenum, bile duct, gastric obstruction)
    • Infection – main indication for therapy
      • Rare in first 2 weeks of illness
        • Bugs: monomicrobial (GNR, enterobacter, gram positive including staph)
        • Clinical: fever, leukocytosis, increasing abdominal pain
        • CT scan: air bubbles in necrotic cavity
      • Therapy (Step Up Approach)
        • 1) Initiation of broad spectrum antibiotics
        • 2) Percutaneous drainage (if patient unstable and unable to wait 4 weeks for collection to wall off)
          • 60% patients with necrotizing pancreatitis can be treated non-invasively with low risk of death
          • Approximately 1/3 will avoid debridement with this approach
        • 3) Minimally invasive debridement after several weeks (if required)
          • Superior to traditional open necrosectomy

Long Term Consequences of AP

  • 20-30% develop exocrine and endocrine dysfunction and chronic pancreatitis occurs in 1/3 to 1/2 of those patients
  • Long-term heavy ETOH as cause and smoking as cofactor dramatically increase transition to chronic pancreatitis

Prevention of Relapse

  • Cholecystectomy (if gallstone pancreatitis) during INITIAL HOSPITALIZATION for MILD pancreatitis reduces rate of subsequent gallstone-related complications by 75% compared with cholecystectomy 25-30 days after discharge
    • Endoscopic biliary spincterotomy reduces (but does not eliminate) risk of recurrent biliary pancreatitis, but may not reduce risk of subsequent acute cholecystitis and biliary colic
  • ETOH use – stop
  • Smoking – stop
  • Tight control of hyperlipidemia – may reduce risk if cause is hypertriglyceridemia

 

Source: NEJM- Acute Pancreatitis

 

Alcoholic Hepatitis Review – Summary

Risk Factors

  • highest risk w/ > 120g ETOH/day (1 drink = 14 g) – 5.7% point prevalence
  •  30-60 g ETOH/day = 1% point prevalence

Clinical Findings

  • Jaundice + liver failure after years of ETOH abuse, typically 40-60 yo
  •  Key clinical finding: rapid onset of jaundice
    • other findings: fever, ascites, proximal muscle loss, encephalopathy (severe cases)
  • Labs: AST:ALT > 2
    • Incr. Cr = indication of hepatorenal syndrome and poor prognosis
  • Expect to have months to years of ascites and hepatic encephalopathy after ETOH abstinence
    • If continued jaundice or onset of renal failure after abstinence – bad news

Histology

  • Mallory Bodies: amorphous eosinophilic inclusion bodies
  • Steatosis: presence of large fat globules in hepatocytes
  • Intrasinusoidal Fibrosis: fibrosis in space between endothelial cells and hepatocyte

Mechanism

  • ETOH -> Acetaldehyde -> Acetate
    • Oxidative metabolism generates reducing equivalents (reduced NAD which is NADH)
    • Incr. NADH blocks fatty acid oxidation & TCA -> Incr. Lipids
  • Gut permeability: altered by ETOH which leads to incr. LPS-endotoxin systemically
    • LPS + Binding protein activate CD14 on Kupffer cells -> activation
  • Kupffer Cell Activation (LPS + CD14 binding): activates CD14 + TLR4 + MD2
    • Downstream actiation of EGR1 (activates TNF-Alpha), NF-kB, TRIF
      • Absence of EGR1 prevents ETOH-induced liver injury in mice
  • Activation of Kupffers leads to free radical production via CYP450 2E1
    • Mitochondrial damage, endoplasmic reticulum apoptosis and lipid synthesis
  • TNF-Alpha = key mediator of hepatocellular injury
    • Decr TNF-R1 = decr. TNF-alpha
    • Seems to target mitochondria -> release of mitochondria cytochrome c & fas ligand
      • Leads to hepatic apoptosis & sensitivity to natural killer T cells

Diagnosis

  • Key Findings: AST:ALT > 2, T Bili > 5, Incr. INR, incr. neutrophils + ASCITES & HX ETOH ABUSE
  • Differential: NASH, viral hep (acute or chronic), toxins, Wilson’s (fulminant), autoimmune, A1AT deficiency, pyogenic hepatic abscess, ascending cholangitis, HCC decompensation
  • Bx is helpful but NOT required for dx or prognosis
  • Screen for bacterial infection: PNA, SBP, UTI

Assessing Severity

  • Maddrey’s, Glasgow and MELD are 3 scores
  • MELD: assesses pt risk of death while waiting for txp
    • Score 21 or greater: 90 day mortality of 20%

Treatment

  • Issues to Address
    • 1) Ascites: sodium restriction, diuretics
    • 2) Hepatic Encephalopathy: lactulose, gut cleansing abx (Rifampin)
    • 3) Vitamin deficiencies: thiamine
    • 4) Delirium Tremens: benzodiazepines
    • 5) Hepatorenal Syndrome: monitor creatinine, albumin + vasoconstrictors (ex. terlipressin, midodrine & octreotide, norepinephrine)
  • Abstinence: most important aspect of tx – psych support, role for baclofen?
  • Corticosteroids: may reduce inflammation in VERY SEVERE CASES ONLY
    • MOA: inhibit activator protein 1 and NF-kB, reduction in proinflammatory cytokines (ex. IL-8, TNF-alpha)
    • Prednisolone 40mg QD x 28 days
    • Indications: Maddrey’s score of 32 or MELD of 21 or greater
    • Calculate Lille score after 7 days of tx – score > 0.45 = no response to steroids & 6 month survival < 25% – unresponsive in 40% steroid cases
  • Pentoxifylline (phosphodiesterase inhibitor): one RCT showing reduced short-term mortality
    • May have a role in decreasing incidence of hepatorenal syndrome
  • What not to give
    • TNF-Alpha inhibitors (Infliximab, Etanercept): may incr. mortality 2/2 infxn
    • Anabolic steroids: no benefit
    • Antioxidants: no benefit
    • Colchicine, PTU, Insulin & Glucagon: no benefit
  • Liver Txp: technically a 6 month wait period of abstinence, but need to eval if mortality is expected to be less than 6 months

 

Source: NEJM – Alcoholic Hepatitis

Fire Related Inhalation Injuries – Summary

Pathophysiology

  • Direct local injury – often SUPRAglottic
    • Infraglottic injury due to inhalation of aerosolized, smaller chemicals – not direct
  • Secondary Inflammation – response of inhalation injury -> ROS formation
    • bronchospasm/vasospasm, bronchorrhea, alveolar flooding, bronchial exudate/cast formation, V/Q mismatch
  • Anoxia
  • CO Exposure – reduced O2 delivery and utilization
    • Carboxyhemoglobin levels
      • 10-20%: headache, nausea
      • 20-30%: muscle weakness, impaired cognition
      • 30-50%: cardiac ischemia, unconsciousness
  • Cyanide – interferes w/ O2 utilization at cytochrome level
    • Persistent acidosis
  • Secondary Infection & Respiration
    • Mucosal slough -> incr. debris in airways & reduced clearance
    • Incr risk of: small airway occlusion, atelectasis, V/Q mismatch, infection

Diagnosis

  • Clinical
    • Burns in enclosed space, cutaneous burns around nose & mouth, singed nasal hair, soot in airway, carbonaceous sputum, hoarseness, wheezing, stridor
  • Bronchoscopy
    • Immediate removal of debris not shown to be useful
      • More useful LATER in course for pulmonary clearance
  • Imaging
    • CXR: usually normal
    • V/Q: inhomogeneous clearing of tracer -> small-airway obstruction & inhalation injury
      • However test is cumbersome and not universally reliable
    • CT Scan: maybe useful for stratification, but not a game changer

Management

  • Early After Exposure (0-72 hours)
    • Cutaneous burns < 20% BSA & no threats to airway patency THEN:
      • elevate HOB, humidify air, observe closely
    • INTUBATE: facial edema, hoarseness/stridor, large cutaneous burns with suspected impending facial edema
      • Bronchospasm – nebulized beta-agonists
      • Prophylactic abx and empirical glucocorticoids NOT advised
      • Early hypoxia -> pressure-control ventilation with PEEP
    • CO Poisoning
      • 100% normobaric O2 x 6 hours
    • Cyanide – persistent acidosis despite hemodynamic normalization
      • Not empirically tested for or treated in most burn centers
      • If suspected -> empiric hydroxycobalamin
  • Intermediate after exposure (3 to 21 days)
    • Mucosal slough + loss of ciliary clearance -> low pulmonary clearance
      • Tx: suctioning, chest physiotherapy, bronchoscopy
        • ? usefulness of nebulized heparin & NAC
    • Intubation > 3 weeks = trach
  • Long-Term
    • Few late complications in most survivors
    • May stem from direct thermal damage, ETT access injury – some may require reconstructive surgery

Source: NEJM – Fire-Related Lung Injuries

Hypoglycemics: Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes – JAMA July 16, 2016 – Volume 316, No. 3

Meta Analysis – evaluating glucose lowering drugs

  • Primary outcome: cardiovascular mortality
  • Secondary outcomes: all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight
  • Tx time: 24 weeks or longer

Methods – 3o7 trials included

  • 177 monotherapy, 109 dual (metformin + other drug), 29 triple (metformin + sulfonylurea + other drug)

Results

  • No significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality
  • Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels.

Takeaway:

  • Monotherapy: Metformin first line, followed by any of the other agents
  • Use patient-centered tx when deciding 2nd line agent
  • ACC perspective: “This is a valuable study, albeit limited by disadvantages inherent to meta-analyses, which established that there are no differences in the associations between glucose-lowering drugs alone or in combination with odds of cardiovascular mortality, all-cause mortality, or myocardial infarction.

Sources:

JAMA – Comparison of Clinical Outcomes/ADRs w/ Glucose Lowering Agents

ACC – Trial summary & perspective

VANISH Trial: Catheter Ablation vs Escalated medical tx in VT

 

NEJM VANISH Study Link 

ACC VANISH Summary

  • The primary outcome of death, ≥3 episodes of ventricular tachycardia within 24 hours, or appropriate ICD shock occurred in 59.1% of the catheter ablation group versus 68.5% of the escalated drug therapy group (p = 0.04).Secondary outcomes: In the ablation group, there were two cardiac perforations and three major bleeds. In the escalated drug therapy group, there were two deaths from pulmonary toxicity and one death from hepatic dysfunction.

2 Minute Medicine Summary

  • 1. Catheter ablation was found to be more effective than escalated antiarrhythmic drug (AAD) therapy at treating patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD) who had ventricular tachycardia (VT) despite AAD therapy.2. The increased effectiveness was only observed in patients treated with amiodarone at baseline.

My Two Cents:

  • Primary outcome statistically significant (p = 0.04), but no apparent difference in overall mortality
    • Primary outcome was a composite of 3 different outcomes
  • Practice correlations: if patient with hx of MI, implantable ICD and currently on amiodarone c/o recurrent shocks, then would send for EP work-up before considering increasing Amiodarone tx
    • If patient not currently on Amiodarone, unable to determine if EP would change outcomes since this study only focused on patients currently on Amiodarone, not other anti-arrhythmic drugs

Acute Liver Failure

Causes

  • Sepsis/shock, viral (HBV) heatstroke, lymphomatic infiltration, Budd-Chiari, toxins (i.e. acetaminophen), ETOH, ischemic hepatopathy, Wilson’s
    • Immunocompromised: HSV, CMV, EBV, VZV
  • Opiates such as oxycodone may slow gut transit leading to increased toxicity of acetaminophen at lower doses than expected

Complications

  • Hepatic encephalopathy (Grade 1 (disordered sleep) through Grade 4 (coma))
    • Tx: lower ICP
      • Hyperosmotic agents (mannitol, hypertonic saline), hyperventilation, hypothermia
      • Lactulose NOT EFFECTIVE in hepatic encephalopathy 2/2 ALF
      • NAC – best used w/ Grade 1-2 hepatic encephalopathy
  • Infection – leading cause of death in ALF
    • Prophylactic abx debatable

Antivirals for HBV ALF

  • Lamivudine – use if tx duration expected to be short
  • Entecavir/tenofovir (more potent agents) – better used for severe, protracted HBV course (defined by increased INR & jaundice x 4 weeks)

Sources:

Animal Bites

Dog Bites

  • No antibiotics necessary – bites are shallow
    • No antibiotics necessary unless signs of systemic or local infection
    • Tx: Augmentin (amoxicillin/claulanate)
  • Pregnant patient
    • Tdap at any point during the pregnancy
    • Per CDC: “Pregnant women should receive Tdap anytime during pregnancy if it is indicated (e.g., wound care, during a community pertussis outbreak).” Just don’t then repeat it again during that same pregnancy.

Cat Bites

  • Antibiotics required due to deep nature of bite
  • Tx: Augmentin

Sources

Ankylosing Spondylitis

Presentation:

  • Age  < 45 yo
  • AM stiffness < 30 minutes – better with movement/exercise
  • Nighttime awakening from pain (second half of night)
  • Key features: inflammatory back pain, enthesitis, dactylitis, uveitis, positive family history for axial spondyloarthritis, IBD, alternating buttock pain, psoriasis, asymmetric arthritis, + response to NSAIDs, elevated CRP or ESR
  • Longtime sxs -> osteoporosis -> increased fx risk

Dx: 3 month hx back pain < 45 yo in addition to below

  • Radiographic Sacroilitis
  • > 4 key features = dx
    • < 4 key features + HLA-B27 = dx
    • < 4 key features + negative HLA + positive MRI = dx
  • 2-3 key features + HLA-B27 = dx
    • 2-3 key feature + negative HLA-B27 + positive MRI = dx
  • 0-1 key feature + HLA-B27 + MRI = dx

Tx:

  • First line: NSAIDs or COX-2 inhibitors
  • Second line (no NSAIDS): TNF-inhibitors
  • Localized sxs: glucocorticoid injections (sparingly)

Sources: