Non-ventilator strategies for ARDS
Place pt on 100% O2 for 5-15 minutes. The Aa Gradient is entirely from shunt. Dive Aa by 20 to get the shunt fraction
Hypoxia=cellular anaerobic metabolism
PAOP <18 or no clinical signs of cardiac etiology
PaO2/FiO2 < 300 (< 200=ARDS)
SpO2/FiO2 ratio to define ALI and ARDS (Chest 2007;132:410) retrospective data to derive and validate S/F ratio of 235 corresponds to P/F ratio of 200 and 315 for 300
Type I alveolar cells are the site of gas exchange, Type II produce Type I and surfactant
In ALI/ARDS, the surfactant gets diluted by protein and fluid, and Type II cells are gone, so can not produce more surfactant causing atelectasis.
Ventilator Induced Lung Injury (VLI)
large tidal volumes or high pressures
can cause an ARDS like picture-ameliorated by PEEP
injury is in dependant areas of the lung=sponge lung
normal lung=baby lung
normal ventilatory pattern causes over-distension of normal lung
NHLBI ARDS network showed increased survival with lower tidal volumes (8% risk reduction)
Proper amount of PEEP is above the lower inflection point of Volume/Pressure curve
? Prone position
Steroids may have a role
ketoconazole may have a role in prevention in at risk populations
the fibroproliferative phase of ARDS is difficult to differentiate from sepsis and pneumonia
fever, leukocytosis, infiltrates, decreased svr can all be seen.
A later reparative phase is characterized by fibroproliferation, and organization of lung tissue If resolution does not occur, disordered collagen deposition occurs leading to extensive lung scarring.These restrictive changes can last for months after the resolution of the acute insult.
The damage to the endothelium and the alveolar epithelium results in the creation of an open interface between the lung and the blood, facilitating the spread of micro-organisms from the lung systemically, stoking up a systemic inflammatory response. Moreover, the injury to epithelial cells handicaps the lungs ability to pump fluid out of airspaces. Fluid filled airspaces, loss of surfactant, microvascular thrombosis and disorganized repair (which leads to fibrosis) reduces resting lung volumes (decreased compliance), increasing ventilation-perfusion mismatch, right to left shunt and the work of breathing. In addition, lymphatic drainage of lung units appears to be curtailed stunned by the acute injury: this contributes to the build up of extravascular fluid. (Neligan)
Intracranial HTN Blood Products Catheter Sepsis Pneumonia/Pulmonary Contusion Cardiopulmonary Bypass Pancreatitis Translocation/Endotoxemia Urosepsis/Amniotic Fluid Embolism Long Bone Fractures
In addition, there are a number of unproven adjunct therapies available, which may, at least in the short term, improve oxygenation: 1. Turn the patient prone this improves ventilation-perfusion matching, although the exact mechanism is unknown (4). 2. Administer inhaled nitric oxide this is a local vasodilator, which dilates up the capillaries around the well-ventilated alveoli, potentially improving ventilation-perfusion matching(5;6). Due to the high cost of administering this agent, nebulized prostacyclin has been used as an alternative. 3. Add almitrine which enhances hypoxic pulmonary vasoconstriction, and may reduce right to left shunt (7). This agent is not available in the USA; phenylephrine can be used instead. Nitric Oxide enhances open alveoli vasodilation
10-20 Parts Per Million
Can cause MetHb, so monitor daily 4. High frequency oscillation full tidal volume ventilation, with no cyclic opening and closing of lung units. Experience with this mode has been very good in pediatric and neonatal practice; there is little published data in adults. 5. Tracheal gas insufflation – 2 or more liters of oxygen are delivered into the major bronchi in expiration to wash out dead space gas. 6. Partial liquid ventilation (PLV) with perfuocarbons, which carry oxygen. This very attractive proposition of liquid PEEP has been underutilized, due to lack of availability. The FRC is filled with the liquid, and the patient ventilated above it. PLV has the added advantage of lavaging the airways and removing cellular debris (7;8). Although of academic interest, this strategy is not currently available. 6. Extracorporeal membrane oxygenation: the patient is put on an extracorporeal circuit and oxygenated by a type of heart-lung bypass machine: there is little evidence of efficacy in adults (9).
Rheumatoid Arthritis and ARDS
a few cases of patients with RA and ARDS. Usually the differential is too wide (unless you grow a monoculture organism out of the sputum) to make a therapeutic decision with out biopsy. I usually start broad-spectrum antibiotics (including PCP until proven otherwise) and, if they don’t turn around in a few days, plan for biopsy.I have been surprised a few times with the finding of BOOP in patients that looked like infectious ARDS. If it is indeed MTX toxicity the prognosis is very guarded
Treatment Protocol. Methylprednisolone or placebo was given daily as intravenous push every 6 hours (one fourth of the daily dose) and changed to a single oral dose when oral intake was restored. A loading dose of 2 mg/kg was followed by 2 mg/kg per day from day 1 to day 14, 1 mg/kg per day from day 15 to day 21, 0.5 mg/kg per day from day 22 to day 28, 0.25 mg/kg per day on days 29 and 30, and 0.125 mg/kg per day on days 31 and 32. If the patient was extubated prior to day 14, treatment was advanced to day 15 of drug therapy and tapered according to schedule.
JAMA. 1998 Jul 8;280(2):159-65. CONCLUSIONS: In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.
But the ARDSNet researchers showed:
routine administration of corticosteroids in ARDS cannot be recommended today, and their use seems harmfulwhen started two weeks or more after onset. Clinical researchmust continue in this area to enhance our understanding of basic mechanisms of lung injury, physiologic defense mechanisms, andtissue repair. Because inflammation plays a central role inthe mechanisms of this disease, therapies to modulate its detrimentaleffect without suppressing its beneficial actions may decreasethe high mortality among patients with ARDS. (NEJM Volume 2006;354:1671-1684)
Improves ventilation in ARDS (Intensive Care Med 2005;31:220)
Amato protective lung strategy (NEJM 1998 338(6):347)
Finally a study that shows mortality benefit from proning early in ARDS (Guerin C, Reignier J, Richard JC, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2013 May 20. (Original) PMID: 23688302 Group(s): the PROSEVA Study Group)
Mt Sinai J Med 2002 Jan/March 73
(Inten Care Med 2005;31:776)
ARDS pts have as much lung as a five-year-old=baby lung
Weight of wet lung and heart squeezes out air=sponge lung
this is why when you prone, new dependent area immediately has CT changes
Rivers editorial as well
improved lung function, improved CNS function, decreased need for sedation, decreased days on vent or in CU
therapy started @ ~48 hours after ICU admit 1000 pts treated for 1 week
EBB and Flow of shock
EBB phase=decreased CO, poor perfusion. Lasts ~3 days
Flow Phase=staccato affair
increased CO, edema, diuresis
Nitric oxide Nitric oxide (NO) has been investigated extensively for use in hypoxic respiratory failure; doses between 1.25 and 40 parts per million (ppm) are generally employed [ 9]. In some, but not all studies, the response to continuous NO treatment can be sustained for days to weeks, but interruptions in treatment or attempts to discontinue NO can worsen oxygenation and increase pulmonary artery pressure [ 6,9-11]. Subsequent work has suggested that patients treated with continuous NO might become sensitized, and require lower doses to achieve improved oxygenation, whereas continued use of higher doses may cause patients to stop responding to NO [ 12].
NO does not help reverse hypoxemia in all patients, and the factors that determine responsiveness are difficult to identify [ 6,7,9,13]. One retrospective study found that patients with septic shock responded less frequently to NO than those without sepsis or septic shock (33 versus 64 percent) [ 14]. A different study reported that a high baseline pulmonary vascular resistance and responsiveness to positive end-expiratory pressure (PEEP) portended a positive response [ 15]. It has also been suggested that NO may have benefits unrelated to improved V/Q matching, including antiinflammatory properties, antiplatelet activity, and effects which diminish vascular permeability [ 13,16-21].
The improvement in V/Q matching due to NO treatment may be magnified by concomitant administration of intravenous almitrine, which enhances hypoxic vasoconstriction and further diminishes shunt [ 22-24]. As an example, one study of 48 consecutive patients with early ARDS found that administration of NO or almitrine increased PaO2 by 75 and 101 mmHg respectively, but by 175 mmHg after administration of both agents [ 23]. However, almitrine is not available in the United States, improvement in oxygen is not universal, and the enhancement of hypoxic vasoconstriction which it produces may elevate pulmonary pressures and diminish right ventricular performance [ 25].
It remains unclear if the beneficial physiologic effects of NO inhalation result in improved patient outcomes. A well-designed multicenter trial randomly assigned 385 patients with moderately severe acute lung injury (P/F ration less than or equal to 250) to placebo versus inhaled NO at 5 ppm. Acute lung injury was not caused by sepsis, and patients had no significant nonpulmonary organ dysfunction at randomization. Although short-term improvements in oxygenation were seen, no benefit on mortality or duration of ventilatory support was demonstrated [ 26].
A prior multicenter, randomized, double blind, placebo-controlled trial compared increasing concentrations of NO with placebo in 177 patients and found that the improvement in oxygenation in patients given NO versus placebo was modest and not sustained ( show table 1) [ 9]. Although not a primary end point in this study, 28-day mortality was not significantly different in the two arms. The marginal response to NO caused one group to argue against further investigation [ 27], although other experts have remained enthusiastic.
In addition, NO may produce toxic radicals, and it is unclear if these are less harmful than subjecting patients to higher fractions of inspired oxygen [ 19]. NO2 and methemoglobin concentrations may increase when high doses of NO are given, and the concentration of both of these species should be monitored at frequent intervals [ 28]. NO also has immunosuppressant properties that theoretically could increase the risk of nosocomial infection, and can cause DNA strand breaks and base alterations that are potentially mutagenic [ 19,29].
Metabolism: Nitric oxide combines with hemoglobin that is 60% to 100% oxygenated. Nitric oxide combines with oxyhemoglobin to produce methemoglobin and nitrate. Within the pulmonary system, nitric oxide can combine with oxygen and water to produce nitrogen dioxide and nitrite respectively, which interact with oxyhemoglobin to then produce methemoglobin and nitrate. At 80 ppm the methemoglobin percent is ~5% after 8 hours of administration. Methemoglobin levels >7% were attained only in patients receiving 80 ppm.
SR/MA shows no mortality benefit (Crit Care Med 2014;42:404)
Patent Foramen Ovale
~20% of ARDS patients have moderate to large shunting through patent foramen ovale (CCM 2010;38:1786)
N Engl J Med. 2010 Sep 16;363(12):1107-16. (Original) PMID: 20843245In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hopitaux de Marseille and the Programme Hospitalier de Recherche Clinique Regional 2004-26 of the French Ministry of