- Email: [email protected]
Acute respiratory distress syndrome in pregnancy
Acute Respiratory Distress Syndrome in Pregnancy James w. Van Hook
Acute respiratory distress syndrome is a serious sequelae of many serious illnesses during pregnancy. An understanding of acute respiratory distress syndrome is central to the proper care of a patient with the disorder. Acute respiratory distress syndrome results in diminished pulmonary compliance and respiratory shunt mediated hypoxemia. Furthermore, the initial pulmonary injury in acute respiratory distress syndrome may be further worsened by therapeutic hyperoxia and barotrauma. Limitation of peak-plateau airway pressure to less than 35 to 40 cm H20 may reduce barotrauma. Inflammatory mediator therapy may hold future promise in attenuation of lung injury induced by acute respiratory distress syndrome. Aggressive care may help those pregnant patients afflicted with acute respiratory distress syndrome. Copyright 9 1997 by W.B. Saunders Company cute respiratory distress s y n d r o m e (ARDS)
A is the often d r e a d e d c o m p a n i o n to m a n y critical illnesses. ARDS carries significant mortality and morbidity in p r e g n a n t and n o n p r e g n a n t individuals. In this article, we will discuss ARDS from the perspective of gas exchange, oxygenation, and mechanical ventilation. We will also highlight particular issues regarding ARDS in pregnancy.
Backgrolmd T h e syndrome of A I ~ S was widely recognized by Ashbaugh et al in 1967.1 Nonetheless , the manifestations ultimately characterized as ARDS were described at least 50 years earlier. 2 An imp o r t a n t caveat concerning AKDS is that it is not a singular etiologic event, but a response to a severe systemic event. Foner et al emphasized the point that AKDS is a localized p u l m o n a r y response to a systemic process, and that the systemic processes predisposing to the developm e n t of ARDS are many. z Consequently, ARDS must be considered in the context of clinical cause (in addition to effect). From the Department of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX. Address reprint requests to James leE. Van Hook, MD, Vice Chief, Maternal-FetalMedicine, Assistant Professcq;Department of Obstetrics & Gynecology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-058Z Copyright9 1997 by W.B. Saunders Company O146-0005/97/2104-0006505. 00/0 320
Acute respiratory distress syndrome has b e e n described in pregnancy. Mabie et al reviewed experience with 16 p r e g n a n t patients with A RDS treated between 1986 and 1992. 4 Maternal mortality was r e p o r t e d at 44%. An abstracted review by Perry et al yielded similar results. 5 The outcomes described in these two series do not appreciably differ f r o m overall mortality with ARDS. Acute respiratory distress syndrome has b e e n r e p o r t e d as a catastrophic e n d p o i n t to obstetric illnesses such as severe preeclampsia, urosepsis, p r e t e r m labor, and hydrops fetalis. 6 In any case, ARDS is certainly recognized in association with obstetric illness. Therefore, a t h o r o u g h understanding of ARDS by the obstetric care provider is important.
Description of A R D S Nonuniformity in the definition of ARDS has m a d e it difficult to c o m p a r e outcomes and treatments. To standardize the definition of AKDS, the American Thoracic Society and the Europ e a n Society of Intensive Care Medicine established by consensus a definition of ARDS. 3"7 Acute respiratory distress syndrome was defined in a c o n t i n u u m with acute lung injury (ALI). Both ALI and ARDS were described as acute diffuse p u l m o n a r y processes in which hydrostatic p u l m o n a r y e d e m a played no direct pathogenetic role. As Table 1 shows, ARDS manifests as the most severe cohort of ALI, with a ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaOz/FiO2) ratio of less than 200. It is
Seminars in Perinatology, Vol 21, No 4 (August), 1997: pp 320-327
Acute Respiratory Distress Syndrome in Pregnancy
TaMe l. Criteria for ARDS 1. 2. 3. 4.
Acute event Noncardiogenic* Chest radiograph--Bilateral infiltrate PaO2/FiO2 < 200
* If used, pulmonary capillarywedge pressure < 19 mm Hg. Abbreviations: PaO2, alveolar partial pressure of oxygen; FiO2, fraction of inspired oxygen. Reprinted with permission from Schuster DP. What is acute lung injury?What is ARDS? Chest 1995;107:1721.
i m p o r t a n t to note that this definition does not involve specific levels of positive and expiratory pressure (PEEP). An operational definition of ARDS (and ALI) encompasses the respiratory consequences actually evident with ARDS. Acute respiratory distress syndrome is clinically characterized by two events-hypoxemia and diminished compliance. Each of these two processes is interrelated and critical to a t h o r o u g h understanding of ARDS management. As follows, are descriptions of diminished compliance and hypoxemia in ARDS. Compliance in A R D S Compliance (C) is a measurement of distensibility. C is therefore couched in terms of change in volume (DV) for a given change in pressure (DP). In Simple terms, pulmonary compliance (CL) is defined as DV/DP. In situations of elevated CL, a small change in pressure will result in a large change in relative lung volume (tidal volume). Conversely, in states of diminished CL, a greater distending pressure gradient is required to achieve a given tidal volume, s Because ARDS is a condition of diminished CL, large changes in pressure are required to produce tidal breathing. Hence, the work required to generate a given minute ventilation (respiratory rate • tidal volume) is increased. This highly elevated work of breathing often causes the spontaneously breathing subject with ARDS to breathe with progressively smaller tidal volumes at increasingly faster rates. This effect, in turn, causes the patient with ARDS who is receiving conventional volume-cycled mechanical ventilation to show elevated ventilatory, pressures.'3 9 1'0 The pressure/volume relationship in lungs is not constant over all possible lung volumes. An optimum range of lung volume is f o u n d in both
3121
normal and abnormal lungs (Fig 1). In ARDS, the normal pressure/volume relationship is altered. Optimum ventilation may occur at a very narrow range of lung volumes in a given patient. This process is particularly important in relationship to hypoxemia in ARDS. Hypoxemia
in A R D S
Ventilation and gas exchange in the lung are not uniform. Gas exchange is affected by the relative a m o u n t of blood flowing to ventilated and nonventilated alveolar units and the n u m b e r of alveolar units being ventilated. The lung is, in effect, made up o f a large n u m b e r of units with varying degrees of ventilation a n d / o r perfusion. West described several " z o n e s " of ventilation/perfusion ratios, s The proportion of alveolar units participating in effective gas exchange is altered by posture, cardiac output, pregnancy, and lung injury. In that ARDS typically involves diffuse bilobar lung injury, the gas exchange manifestations of ARDS are atelectasis and shunt. If, as a result of lung injury, alveolar segments b e c o m e atelectailc, they do not participate in gas exchange. Even more importantly, nonventilated segments are often still perfused, producing nonoxygenated shunt segments, s-l~ Also, because each shunt segment is not distended, the compliance of each shunt segment is lower than in neighboring nonatelectatic segments. Inspired gas therefore preferentially flows to open segments.
11) Eo >
0
I
0
I
I
I
[
Distending pressure
Figure 1. Comparison of pressure-volume relationship in normal (a) and ARDS (b) subject. For a given tidal volume, distending pressure is greater. Also, the range of attainable lung volumes is less with ARDS.
322
James W. Van Hook
Although i t is obviously advantageous for inspired gas to flow to functioning alveolar units, overdistention of those units may both reduce effective gas exchange !by alteration of the "West z o n e " of the alveoli) and may propagate lung injury by overdistention barotrauma. 8a~ It is important to recognize the pernicious interrelation between diminished compliance and atelectasis. In that atetectatic units have diminished compliance, work of breathing is increased. The consequence of increased work of breathing is a gradual decrease in tidal volume in spontaneously breathing ARDS patients. Decreased tidal volume breathing produces more atelectasis. Compliance is diminished even further. Work of breathing is yet again increased. Tidal volume decreases yet again. If unchecked, this self-perpetuating process inevitably progresses to respiratory failure. Conversely, one of the tenets of treatment in ARDS is to prevent or reduce atelectasis and to accomplish gas exchange at an optimal tidal volume.
Pathophysiology of ARDS Simply stated, the pathogenesis of ARDS results from immune-system activation in response to an injury or event. In the case of ARDS, the target organ of the body's i m m u n e system is the lung. Inflammatory mediators damage pulmonary epithelial and endothelial tissues. An increase in vascular permeability results. Acutely, the increase in permeability produces atelectasis and diminished compliance, as stated previously. Pulmonary shunt and hypoxemia ensue. Secondarily, extensive neutrophil infiltration occurs to the alveolar units. Neutrophil infiltration of alveoli causes extensive collateral damage to relatively unaffected gas-exchange units. Approximately 10 to 14 days after the initial insult, resolution of the acute process l~egins. In severe cases, collagen deposition, fibrosis, and scarring may invoke chronic respiratory insufficiency, a~ Therefore, ARDS is, if nothing else, an inflammatory event with manifestations not unlike those found in o{her organ systems of patients with systemic inflammatory response syndrome. Ideal treatment of ARDS would theoretically involve support during the acute insult, limitation of collateral pulmonary damage, and host-support during recovery. Most ventilatory support of ARDS patients is aimed at support and limita-
Table 2. Treatment Goals of ARDS Limitation of lung injury Correction of underlying process Prevention of complications Nutritional support
tion of collateral damage. O t h e r therapies are usually directed toward host-support during recovery.
Treatment Concepts in ARDS As described previously, successful treatment of ARDS entails support and resolution of whatever underlying process initiated the ARDS. In that context, we will discuss the general aspects of ARDS treatment. Overall treatment goals are outlined in Table 2 which stresses, as important concepts, the limitation of injury to the lungs and the overall support provided until the underlying process is corrected or resolves. ARDS is, above all things, a pulmonary response to a systemic process.
VentUatory Support In that both hypoxemia and gas exchange are impaired in ARDS, most patients with ARDS require mechanical ventilation. Extensive research has been conducted on the practice of mechanical ventilation in ARDS. At present, no m e t h o d of mechanical ventilation has been shown to be clearly superior in the treatment of ARDS. Nonetheless, in an effort to limit ARDS lung injury, several basic principles of mechanical ventilation are to be considered. 12 Lung injury in ARDS is diffuse yet nonuniform. Ventilation of the ARDS-affected lung will therefore preferentially occur in relatively unaffected alveolar units (Fig 2). 1~ If a relatively high tidal volume is used for volume ventilation, overdistention of relatively unaffected lung units may induce collateral damage. 14Mechanical ventilation of the ARDS patient usually involves some strategy to limit overdistention of relatively unaffected lung units. One of the most straightforward techniques to limit collateral damage is to simply volume ventilate at lower tidal volumes. Traditional postoperative ventilation of the healthy lung is often undertaken at 12 to 15 m L / k g tidal volumes. If
Acute Respiratory Distress Syndrome in Pregnancy
No PEEP
~
Alveolar recruitment
Overdistention
Figure 2. The effect of PEEP on alveolar recruitment, without (A) and with (B) PEEP. Overdistention (C) will result in deleterious effects on intact lung units.
large tidal volume ventilation is used in the face of diffuse ARDS, markedly increased ventilatory pressures will he seen, Use of a lower tidal volu m e (eg, 5 to 8 m L / k g ) may limit p u l m o n a r y barotrauma. 15'16Animal models ~bfARDS suggest that plateau-peak airway pressures of greater than 35 cm H 2 0 appreciably increase barot r a u m a in relatively unaffected alveolar segments. 12'14'1c~8 In summation, one goal of conventional ventilation in ARDS is to limit, if possible, peak-plateau airway pressure to less than 35 cm H20.12 Low tidal volume conventional ventilation may adversely affect the relative contribution that dead space makes in tidal breathing. A lower tidal volume at a given respiratory rate will pro-
323
duce a lower minute volume (respiratory rate • tidal volume). To maintain a given minute volume, respiratory rate must be increased as tidal volume is reduced. At low tidal volumes, a relatively larger portion of a given inspiration involves dead space ventilation. Because dead space ventilation is not effective in gas exchange, low tidal volume breathing becomes progressively less effective in gas exchange. 8 Acute respiratory distress syndrome itself is a circumstance in which dead space ventilation is increased. 9'1~ Low tidal ventilation may therefore significantly exaggerate the already affected dead space-tidal volume relationship of the injured ARDS lung. Pressure-controlled ventilation has b e e n used in an effort to reduce p e a k plateau airway pressure. By ventilating lungs to a given pressure, gas flow, and inspiratory time and rate may be used to affect tidal breathing. Reversal of the n o r m a l 1:1.3 ratio of inspiration to expiration is often a t t e m p t e d in the context of pressure-controlled ventilation. "Inverse ratio pressure controlled ventilation" may allow reduction in peak airway pressure (at the expense of m e a n airway pressure). 19 Although this technique holds m u c h promise, it has not yet b e e n shown to reduce the mortality observed in adult patients with ARDS. 12'2~ Airway pressure release ventilation and high frequency ventilation have also had largely inconclusive results in the t r e a t m e n t of ARDS. In an effort to limit barotrauma, m a n y clinicians elect to modify the "physiological" treatm e n t goals of normal-range arterial blood gases when caring for mechanically ventilated ARDS patients. Permissive h y p e r c a p n e a and the tolerance of relatively low PaO2 levels are used in an effort to limit tidal volume-induced barotrauma, hyperoxia, and the necessity for high levels of PEEP. Once again, these techniques hold p r o m ise, but their impact on survival in ARDS is, as o f yet, unproven, a2 Extracorporal membrane oxygenation (ECMO) was first used in the t r e a t m e n t of ARDS m o r e than 20 years ago. As with the techniques previously mentioned, the promise ECMO holds in ARDS m a n a g e m e n t revolves a r o u n d ECMO's potential ability to limit b a r o t r a u m a through very limited use of the ECMO/ARDS patient's own lungs during the most severe stages of ARDS. In that ECMO is highly successful in children, the National Institutes of Health sponsored
324
James W.. Van Hook
multicenter trials of ECMO in adult patients with ARDS. 22'23 In that outcome was not appreciably different from the conventionally ventilated control group, ECMO was not d e e m e d superior/1'23 Nonetheless, ECMO may have a defined place in the treatment of some patients with ARDS. It is h o p e d that newer trials may identify particular candidates who may benefit from ECMO. Other techniques tried in ARDS include intravenous oxygenation, inhaled nitric oxide, computer-modulated mechanical ventilation, exogenous surfactant administration, high frequency ventilation, and partial liquid ventilation. 21'24'25 Partial liquid ventilation with perfluorochemicals is particularly promising in that it may be both anti-inflammatory and barotrauma-protectire. 26 Trials are currently underway concerning partial liquid ventilation in ARDS.
Anti-inflammatory Therapy As implied earlier in this review, ARDS encompasses the process of diffuse propagated inflammatory injury to the lung. Consequently, several treatment strategies have been investigated to potentially modulate the inflammatory process activated in ARDS. As mentioned previously, inhaled nitric oxide (NO) has been used in the mechanical ventilation of ARDS patient. 25'27 Inhaled NO will decrease pulmonary artery pressure and increase arterial oxygenation by selectively dilating pup monary vessels in ventilated alveolar segments o f the lung. The feasibility of NO ventilation in ARDS was investigated by Rossaint et al in 1993. 25 One unresolved issue with NO administration involves its potential for injury propagation through its function as a free radical. 2s In that NO may both propagate oxidation and, in certain instances, be instrumental in termination of lipid peroxidation chain propagation, the optim u m use of NO as both an aid to mechanical ventilation a n d / o r a mediator of inflammation is unresolved. 2s-31 Anti-inflammatory treatment of ARDS with more clinically available agents has also been investigated. Corticosteroids seem to offer no benefit (and perhaps some harm) to ARDS patients treated with those agents. 32 T h r o u g h inhibition of platelet aggregation, limitation of lysosomal enzyme release, and suppression of polymorphoneutrophil chemotaxis, prostaglandin E1 (PGE~) was thought to be potentially useful in ARDS
propagated inflammatory injury. Unfortunately, Bone e t al failed to show any demonstrable benefit in survival from PGE1 administration in ARDS. 33 Cyclooxygenase inhibitors, such as ibuprofen, display some positive effect on animals with ARDS. Randomized h u m a n trials have shown some improvement in ventilatory support indices, but fail to impart any appreciable survival advantage with their use. 34'35 The antifungal agent ketoconazole has pharmacological activity as an inhibitor of leukotriene and thromboxane synthesis. Although the efficacy of ketoconazole in treatment is unclear, at least one study has shown a reduction of the incidence of ARDS in at-risk patients prospectively treated with ketoconazole, a6 Other agents, such as pentoxifylline, also may reduce the incidence of ARDS in at-risk patients. 28'~7 In summation, various pharmocological agents have been used to attenuate the progression of ARDS. At present, no single agent or treatment has reliably improved outcome in patients with ARDS. It is h o p e d that further research will illuminate effective anti-inflammatory treatment for ARDS.
Management of ARDS in Pregnancy Compared with ARDS m a n a g e m e n t during nonpregnancy, m a n a g e m e n t during pregnancy is simultaneously similar and different. Several issues of ARDS care during pregnancy will be discussed in the following section.
Oxygenation and Acid Base As m e n t i o n e d previously, in an effort to limit pulmonary barotrauma, traditional wisdom in arterial blood gas interpretation has generally been supplanted by a philosophy of nonphysiological tolerance of at least some degree of acidbase abnormalities and relative hypoxemia in adult ARDS management. Permissive hypercapnea, limitation of PEEP (at the expense of PaO2) and low minute volume breathing have all been used. Pregnancy may place some constraints on nonphysiological arterial blood gas goals. As m e n t i o n e d elsewhere in this issue, pregnancy normally induces a state of compensated respiratory alkalosis. Therefore, arterial partial pressure of oxygen (PaCO2), is normally 5 to 10 m m Hg less during pregnancy than it is in n o n p r e g n a n t
Acute Respiratory Distress Syndrome in Pregnancy
subjects. 38 Uteroplacental perfusion has been shown to be reduced in the circumstance of even lower PaCO2. 39 More germane to ARDS treatm e n t in ,pregnancy is the potential for fetal acidbase d e r a n g e m e n t from" the use of permissive hypercapnea (and the concomitant respiratory acidosis) in ARDS ventilator management. Therefore, until more data are available, we generally endeavor to maintain relatively physiological PaCO2 levels during mechanical ventilation of pregnant ARDS patients. The issue of PaO2 is less clear. It is postulated that placental transfer of oxygen is venous oxygen content-mediated. Although maternal arterial oxygen content is not appreciably increased at PaO2 levels above 60 m m Hg (and infinitesimally increased at PaO2 levels greater than 100 m m Hg), maternal venous oxygen content is somewhat increased at higher PaO2 levels. Because elevated venous content could favorably influence placental oxygen delivery, many clinicians think that supranormal PaO2 levels (such as those observed in healthy p r e g n a n t patients receiving supplemental oxygen) might augment transplacental fetal oxygen delivery. However, both the increase in maternal 2,3-diphosphoglycerate and the relatively increased affinity of fetal hemoglobin for oxygen tend to support at least some degree of maternal-fetal tolerance for relative hypoxia. 6'39'4~We therefore think that 60 m m Hg is a reasonable goal in pregnant patients with ARDS. Data from pregnant women studied at high altitude support the concept that fetal oxygen delivery is adequate at PaO2 levels of 60 m m Hg. 41 A final acid-base issue to consider in the care of the critically ill ARDS obstetric patient involves serum HCOs. Because pregnancy is a compensated acid-base state, HCO~ decreases. Consequently, serum-buffering capacity is decreased during pregnancy. Therefore, any intrinsic (disease state-mediated) or iatrogenic inducers of metabolic or respiratory acidosis may potentially be less well-tolerated in pregnancy.
Mechanical Ventilation A complete discussion of mechanical ventilation in pregnancy is beyond the scope of this article. Nonetheless, several important )ssues deserve discussion. The decision to mechanically ventilate a pregnant patient with ARDS should ideally be made in such a way as to (if possible!) allow
325
the elective intubation of the patient. Because pregnant patients usually are relatively young and often otherwise reasonably healthy, they may be able to tolerate periods of high work of breathing spontaneous ventilation somewhat better than the typical intensive care patient with ARDS. Unfortunately, the very tolerance of severe lung disease may predispose the pregnant patient to profound, rapidly progressive respiratory failure once her physiological reserve is expended. Also, the progressively smaller tidal volumes observed in developing increased work of breathing respiratory failure may potentiate atelectasis from the normally diminished functional residual volume observed in pregnancy. Supine positioning further aggravates this process. Finally, arterial blood gas interpretation should be made in the context of what is normal for pregnancy. Ergo, a normal (for n o n p r e g n a n t individuals) PaCO2 may be indicative of ventilatory failure in a pregnant patient. A " n o r m a l " pulseoximetry reading may not become abnormal until after respiratory failure o c c u r s . 42 In any case, careful observation for impending respiratory failure should be part of the care for any unintubated pregnant patient with acute lung injury or ARDS. Little data are available regarding the use of specific techniques o f ventilation in pregnant ARDS patients. At our institution, we routinely administer mechanical ventilation to pregnant patients in a dedicated unit within our labor and delivery area. We generally use conventional volume-cycled mechanical ventilation as our initial modality. When we are unable to maintain PaO2 of at least 60 to 65 m m Hg on 50% or less inspired oxygen, we use PEEP in amounts of up to 15 cm H20. When peak plateau inspiratory pressure is consistently above 35 to 40 c m H 2 O , we use pressure-controlled ventilation. Because pregnant patients with ARDS often have potentially reversible disease processes, they may therefore represent a subgroup of ARDS victims who may benefit from aggressive use of advanced techniques and measures. Individualization of care is key. Fluid Management Two schools of thought exist regarding fluid m a n a g e m e n t in n o n p r e g n a n t patients with ARDS. If considered strictly from a pulmonary standpoint, reduction in lung water and im-
326
James W.. Van Hook
provemenls in gas exchange, compliance, and oxygenation can be accomplished with fluid restriction and relative hypovolemia. However, because many cases of ARDS are associated with multisystem dysfunction or sepsis, body tissue perfusion and collateral organ d a m a g e may occur with hypovolemia or hypoperfusion. Therefore, fluid homeostasis and therapy in ARDS is usually, at best, a compromise between lung water and organ perfusionP '11 Pregnancy, of course, alters this compromise between perfusion and lung water by introducing another organ system, the placenta. Most obstetric providers recognize the limited tolerance of the fetoplacental unit to hypovolemia. Volume homeostasis in the p r e g n a n t individual in effect becomes a three-way compromise involving lung water, maternal perfusion and fetal perfusion, and oxygen delivery. Fetal heart rate monitoring may offer a surprising measure of relative intravascular volume status in the pregnant individual, as Invasive h e m o d y n a m i c monitoring, if used, may allow the optimization of this compromise. O u r developed philosophy has entailed relative fluid restriction provided that fetal tolerance is evident, metabolic acidosis is not present, renal and other organ perfusion is maintained, vasopressors are not required, and hemodynamically influential modes of mechanical ventilation are n o t required. If these conditions cannot be met with relative fluid restriction, empirical volume administration a n d / o r invasive monitoring is usually required.
Sedation/Paralysis/Nutrition Sedation a n d / o r pain relief is usually advisable in the care of intubated patients with ARDS. In addition to providing for patient comforq sedation and pain relief may reduce maternal oxygen consumption and lessen the effects any given m o d e of ventilation may have "on the developm e n t of barotrauma. Nondepolarizing skeletal muscle paralysis (along with sufficient sedation) may be required if advanced modes of ventilation are necessary. Proper monitoring and the recognition of potential complications involved with paralysis are r e c o m m e n d e d if paralysis is used. Because ARDS may require several days (or weeks) of intubated care, nutritional support is very important. If possible, enteral feeding is preferred and may reduce the translocation of gastrointestinal bacteria into the body. Because
of the additional nutritional requirements of pregnancy, indirect calorimetry may be advisable for the long-term monitoring of the enterally or parenterally fed p r e g n a n t patient.
Conclusion ARDS presents a set of unique challenges to the providers faced with a critically ill obstetric patient. Recognition of the special circumstances involved in pregnancy are central to the p r o p e r care of the p r e g n a n t patient with ARDS. As necessary, multidisciplinary care with early referral to an appropriate tertiary care center will optimize the o u t c o m e in this serious disorder. Finally, recognition of the often-reversible nature of some cases of ARDS during pregnancy may foster a clinician's pursuit of advanced therapeutic opportunities.
References 1. Ashbaugh DG, BigelowDB, Petty DB: Acute respiratory distress in adults. Lancet 2:319-323, 1967 2. Taylor RW, Duncan CA: The adult respiratory distress syndrome. Res Medica 1:17-24, 1983 3. Foner BJ, Norwood SH, Taylor RW: The acute respiratory distress syndrome, in CivettaJM, Taylor RW, Kirby RR (eds): Critical Care, ed 3. Philadelphia, PA, Lippincott~Raven, 1997, pp 1825-1840 4. Mahie WC, Barton JR, Sibai BM; Adult respiratory distress syndrome in pregnancy. Am J Obstet Gynecol 167:950-957, 1992 5. Perry KG, Martin RW, Blake PG, et al: Maternal outcome associated with adult respiratory distress syndrome. Am J Obstet Gynecol 174:391, 1996 (abstr) 6. Cunningham FG, MacDonald PC, Gant NF, et ah Williams Obstetrics, ed 20. Stamford, CT, Appleton & Lange, 1997 7. The American-European Consensus Conference on ARDS. AmJ Respir Crit Care Med 149:818-824,1994 8. WestJB:RespiratoryPhysiology-TheEssentials, ed 5. Baltimore, MD, Williams & Wilkins, 1995 9. ShoemakerWC, Appel PL: Pathophysiologyof adult respiratory distress syndromeafter sepsis and surgicaloperations. Crit Care Med 13:166-172, 1985 10. Gattinoni L, Bombino M, Pelosi P, et ah Lung structure and function in different stages of severe adult respiratory distress sYndrome.JAMA271:1772-1779, 1994 11. Gropper MA, Weiner-KronishJP: Acute lung injury and acute respiratorydistress syndrome, in MurrayMJ, Coursin DB, Pearl RG, Prough DS (eds): Critical Care Medicine: Perioperative Management. Philadelphia, PA, Lippincott-Raven, 1997, pp 441451 12. SlutskyAS, Brochard L, Dellinger, et al: ACCPconsensus conference-mechanical ventilation. Chest 104:18331859, 1993
Acute Respiratory Distress Syndrome in Pregnancy
13. Gattino.ni L, Pesenti A, Bombino M, et al: Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure. Anesthesiology 69:824-832, 1988 14. Finger S, Rocker G: Alveolar overdistention is an important mechanism of persisfent lung damage following severe protracted ARDS. Anaesth Intens Care 24:569573, 1996 15. Hickling K: Low mortality associated with low volume pressure limited ventilation with permissive hypercapnea in severe adult respiratory distress. Intensive Care Med 16:372-377, 1990 16. Fu Z, Costello ML, Tsukimoto K, et al: High lungvolume increases stress failure in pulmonary capillaries. J Appl Physiol 73:123-133, 1992 17. ParkerJC, Hernandez LA, Peevy KJ: Mechanisms ofventilatol~induced lung injury. Crit Care Med 21:131-143; 1993 18. Dryfuss D, Basset G, Soler P, et ah Intermittent positivepressure hyperventilation with high inflation pressuresproduces pulmonary microvascular injury in rats. Am Rev Respir Dis 132:880-884, 1985 19. Lain DC, DiBenedetto R, Morris SL, et al: Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation. Chest 95:1081-1088, 1989 20. Morris AH, Wallace CJ, Clemmer TP, et al: Final report: Computerized protocol controlled clinical trial of new therapy which includes ECCO2-R for ARDS. Am Rev Respir Dis 142(Part 2):A184 (absrr) 21. Morris AH: Adult respirator5, distress syndrome and new modes of mechanical ventilation: reducing the complications of high volume and high pressure. New Horizons 2:19-33, 1994 22. Anderson HL III, Bartlett RH: Extracorporeal and intravascular gas exchange devices, in Ayres SM, Gsenvik A, Holbrook PR, Shoemaker WC (eds): Textbook of Critical Care, ed 3. Philadelphia, PA, WB Saunders, 1995, pp 943-951 23. Morris AH, Wallace CJ, Menlove RL, et al: Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 149:295-305, 1994 24. Conrad SA, EggerstedtJM, Morris VF, et al: Prolonged intracorporeal support of gas exchange with an intravenacaval oxygenator. Chest 103:158-161, 1993 25. Rossaint R, Falke KJ, Lopez F, et ah Inhaled nitric oxide for the adult respiratory distress synttrome. N EnglJ Med 328:339-405, 1993 26. Hirschl RB, Parent A, Tooley R, et al: Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure. Ann Surg 221:7988, 1995 27. Krafft P, Fridrich P, Fitzgerald RD, et ah Effectiveness of
327
nitric oxide inhalation in septic ARDS. Chest I09:486493, 1996 28. Louie S, Halliwell B, Cross CE: Adult respiratory distress syndrome: A radical perspective. Adv Pharmacol 38:457490, 1997 29. Darley-Usmar V, Wiseman H, Halliwell B: Nitric oxide and oxygen radicals: A question of balance. FEBS Lett 369:131-135, 1995 30. Wink DA, Cook JA, Pacelli R, et ah Nitric oxide (NO) protects against cellular damage by reactive oxygen species. Toxicol Lett 82:221-226, 1995 31. Moncada S, Higgs EA: Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEBJ 9:13191330, 1995 32. Bernard GR, LuceJM, Sprung CL, et al: High dose corticosteroids in patients with adult respiratory distress syndrome. N EnglJ Med 317:1565-1570, 1987 33. Bone RC, Slotman G, Maunder R, et al: Randomized double-blind multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Chest 96:114-119, 1989 34. Haupt MT, Jastremski MS, Clemmer TP, et al: The ibuprofen study group: effect of ibuprofen in patients with severe sepsis. A randomized double-blind, multicenter srudy. Crit Care Med 19:1339-1347, 1991 35. Bernard GR, Wheeler AP, Russell JA, et al: The effects of ibuprofen on the physiology and survival of patients with sepsis. N EnglJ Med 336:912-918, 1997 36. Yu M, Tomasa G: A double-blind, prospective, randomized trial of ketoconazole, a thromboxane synthetase inhibitor, in the prophylaxis of the adult respiratory distress syndrome. Crit Care Med 21:1635-1642, 1993 37. Montravers P, Fagon ]Y, Gilbert C, et al: Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory distress syndrome. Chest 103:1017-1022, 1993 38. Van HookJW, Owens TM: Care of critically ill obstetric patients, in Murray MJ, Coursin DB, Pearl RG, Prough DS (eds): Critical Care Medicine: Perioperative Management. Philadelphia, PA, Lippincott-Raven, 1997, pp 733743 39. Levinson G, Shnider SM, DeLorimier AA, et al: Effects of maternal hyperventilation on uterine blood flow and fetal oxygenation and acid-base status. AnesthesioloN~ 40:340-347, 1974 40. Rorth M, Brahe NE: 2,3-Diphosphoglycerate and creatine in the red cell during human pregnancy. Scand J Clin Lab Invest 28:271-276, 1971 41. Sobrevilla LA, Cassinelli MT, Carcelen A, et al: Human fetal and maternal oxygen tension and acid-base status during delivery at high altitude. Am ] O b s t e t Gynecol 111:1111-1118, 1971 42. Van HookJW, Harvey CJ, Anderson GD: Effect of pregnancy on maternal oxygen saturation values: Use of reflectance pulse oximetry during pregnancy. South Med J 89:1188-1192, 1996
Acute respiratory distress syndrome is a serious sequelae of many serious illnesses during pregnancy. An understanding of acute respiratory distress syndrome is central to the proper care of a patient with the disorder. Acute respiratory distress syndrome results in diminished pulmonary compliance and respiratory shunt mediated hypoxemia. Furthermore, the initial pulmonary injury in acute respiratory distress syndrome may be further worsened by therapeutic hyperoxia and barotrauma. Limitation of peak-plateau airway pressure to less than 35 to 40 cm H20 may reduce barotrauma. Inflammatory mediator therapy may hold future promise in attenuation of lung injury induced by acute respiratory distress syndrome. Aggressive care may help those pregnant patients afflicted with acute respiratory distress syndrome. Copyright 9 1997 by W.B. Saunders Company cute respiratory distress s y n d r o m e (ARDS)
A is the often d r e a d e d c o m p a n i o n to m a n y critical illnesses. ARDS carries significant mortality and morbidity in p r e g n a n t and n o n p r e g n a n t individuals. In this article, we will discuss ARDS from the perspective of gas exchange, oxygenation, and mechanical ventilation. We will also highlight particular issues regarding ARDS in pregnancy.
Backgrolmd T h e syndrome of A I ~ S was widely recognized by Ashbaugh et al in 1967.1 Nonetheless , the manifestations ultimately characterized as ARDS were described at least 50 years earlier. 2 An imp o r t a n t caveat concerning AKDS is that it is not a singular etiologic event, but a response to a severe systemic event. Foner et al emphasized the point that AKDS is a localized p u l m o n a r y response to a systemic process, and that the systemic processes predisposing to the developm e n t of ARDS are many. z Consequently, ARDS must be considered in the context of clinical cause (in addition to effect). From the Department of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX. Address reprint requests to James leE. Van Hook, MD, Vice Chief, Maternal-FetalMedicine, Assistant Professcq;Department of Obstetrics & Gynecology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-058Z Copyright9 1997 by W.B. Saunders Company O146-0005/97/2104-0006505. 00/0 320
Acute respiratory distress syndrome has b e e n described in pregnancy. Mabie et al reviewed experience with 16 p r e g n a n t patients with A RDS treated between 1986 and 1992. 4 Maternal mortality was r e p o r t e d at 44%. An abstracted review by Perry et al yielded similar results. 5 The outcomes described in these two series do not appreciably differ f r o m overall mortality with ARDS. Acute respiratory distress syndrome has b e e n r e p o r t e d as a catastrophic e n d p o i n t to obstetric illnesses such as severe preeclampsia, urosepsis, p r e t e r m labor, and hydrops fetalis. 6 In any case, ARDS is certainly recognized in association with obstetric illness. Therefore, a t h o r o u g h understanding of ARDS by the obstetric care provider is important.
Description of A R D S Nonuniformity in the definition of ARDS has m a d e it difficult to c o m p a r e outcomes and treatments. To standardize the definition of AKDS, the American Thoracic Society and the Europ e a n Society of Intensive Care Medicine established by consensus a definition of ARDS. 3"7 Acute respiratory distress syndrome was defined in a c o n t i n u u m with acute lung injury (ALI). Both ALI and ARDS were described as acute diffuse p u l m o n a r y processes in which hydrostatic p u l m o n a r y e d e m a played no direct pathogenetic role. As Table 1 shows, ARDS manifests as the most severe cohort of ALI, with a ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaOz/FiO2) ratio of less than 200. It is
Seminars in Perinatology, Vol 21, No 4 (August), 1997: pp 320-327
Acute Respiratory Distress Syndrome in Pregnancy
TaMe l. Criteria for ARDS 1. 2. 3. 4.
Acute event Noncardiogenic* Chest radiograph--Bilateral infiltrate PaO2/FiO2 < 200
* If used, pulmonary capillarywedge pressure < 19 mm Hg. Abbreviations: PaO2, alveolar partial pressure of oxygen; FiO2, fraction of inspired oxygen. Reprinted with permission from Schuster DP. What is acute lung injury?What is ARDS? Chest 1995;107:1721.
i m p o r t a n t to note that this definition does not involve specific levels of positive and expiratory pressure (PEEP). An operational definition of ARDS (and ALI) encompasses the respiratory consequences actually evident with ARDS. Acute respiratory distress syndrome is clinically characterized by two events-hypoxemia and diminished compliance. Each of these two processes is interrelated and critical to a t h o r o u g h understanding of ARDS management. As follows, are descriptions of diminished compliance and hypoxemia in ARDS. Compliance in A R D S Compliance (C) is a measurement of distensibility. C is therefore couched in terms of change in volume (DV) for a given change in pressure (DP). In Simple terms, pulmonary compliance (CL) is defined as DV/DP. In situations of elevated CL, a small change in pressure will result in a large change in relative lung volume (tidal volume). Conversely, in states of diminished CL, a greater distending pressure gradient is required to achieve a given tidal volume, s Because ARDS is a condition of diminished CL, large changes in pressure are required to produce tidal breathing. Hence, the work required to generate a given minute ventilation (respiratory rate • tidal volume) is increased. This highly elevated work of breathing often causes the spontaneously breathing subject with ARDS to breathe with progressively smaller tidal volumes at increasingly faster rates. This effect, in turn, causes the patient with ARDS who is receiving conventional volume-cycled mechanical ventilation to show elevated ventilatory, pressures.'3 9 1'0 The pressure/volume relationship in lungs is not constant over all possible lung volumes. An optimum range of lung volume is f o u n d in both
3121
normal and abnormal lungs (Fig 1). In ARDS, the normal pressure/volume relationship is altered. Optimum ventilation may occur at a very narrow range of lung volumes in a given patient. This process is particularly important in relationship to hypoxemia in ARDS. Hypoxemia
in A R D S
Ventilation and gas exchange in the lung are not uniform. Gas exchange is affected by the relative a m o u n t of blood flowing to ventilated and nonventilated alveolar units and the n u m b e r of alveolar units being ventilated. The lung is, in effect, made up o f a large n u m b e r of units with varying degrees of ventilation a n d / o r perfusion. West described several " z o n e s " of ventilation/perfusion ratios, s The proportion of alveolar units participating in effective gas exchange is altered by posture, cardiac output, pregnancy, and lung injury. In that ARDS typically involves diffuse bilobar lung injury, the gas exchange manifestations of ARDS are atelectasis and shunt. If, as a result of lung injury, alveolar segments b e c o m e atelectailc, they do not participate in gas exchange. Even more importantly, nonventilated segments are often still perfused, producing nonoxygenated shunt segments, s-l~ Also, because each shunt segment is not distended, the compliance of each shunt segment is lower than in neighboring nonatelectatic segments. Inspired gas therefore preferentially flows to open segments.
11) Eo >
0
I
0
I
I
I
[
Distending pressure
Figure 1. Comparison of pressure-volume relationship in normal (a) and ARDS (b) subject. For a given tidal volume, distending pressure is greater. Also, the range of attainable lung volumes is less with ARDS.
322
James W. Van Hook
Although i t is obviously advantageous for inspired gas to flow to functioning alveolar units, overdistention of those units may both reduce effective gas exchange !by alteration of the "West z o n e " of the alveoli) and may propagate lung injury by overdistention barotrauma. 8a~ It is important to recognize the pernicious interrelation between diminished compliance and atelectasis. In that atetectatic units have diminished compliance, work of breathing is increased. The consequence of increased work of breathing is a gradual decrease in tidal volume in spontaneously breathing ARDS patients. Decreased tidal volume breathing produces more atelectasis. Compliance is diminished even further. Work of breathing is yet again increased. Tidal volume decreases yet again. If unchecked, this self-perpetuating process inevitably progresses to respiratory failure. Conversely, one of the tenets of treatment in ARDS is to prevent or reduce atelectasis and to accomplish gas exchange at an optimal tidal volume.
Pathophysiology of ARDS Simply stated, the pathogenesis of ARDS results from immune-system activation in response to an injury or event. In the case of ARDS, the target organ of the body's i m m u n e system is the lung. Inflammatory mediators damage pulmonary epithelial and endothelial tissues. An increase in vascular permeability results. Acutely, the increase in permeability produces atelectasis and diminished compliance, as stated previously. Pulmonary shunt and hypoxemia ensue. Secondarily, extensive neutrophil infiltration occurs to the alveolar units. Neutrophil infiltration of alveoli causes extensive collateral damage to relatively unaffected gas-exchange units. Approximately 10 to 14 days after the initial insult, resolution of the acute process l~egins. In severe cases, collagen deposition, fibrosis, and scarring may invoke chronic respiratory insufficiency, a~ Therefore, ARDS is, if nothing else, an inflammatory event with manifestations not unlike those found in o{her organ systems of patients with systemic inflammatory response syndrome. Ideal treatment of ARDS would theoretically involve support during the acute insult, limitation of collateral pulmonary damage, and host-support during recovery. Most ventilatory support of ARDS patients is aimed at support and limita-
Table 2. Treatment Goals of ARDS Limitation of lung injury Correction of underlying process Prevention of complications Nutritional support
tion of collateral damage. O t h e r therapies are usually directed toward host-support during recovery.
Treatment Concepts in ARDS As described previously, successful treatment of ARDS entails support and resolution of whatever underlying process initiated the ARDS. In that context, we will discuss the general aspects of ARDS treatment. Overall treatment goals are outlined in Table 2 which stresses, as important concepts, the limitation of injury to the lungs and the overall support provided until the underlying process is corrected or resolves. ARDS is, above all things, a pulmonary response to a systemic process.
VentUatory Support In that both hypoxemia and gas exchange are impaired in ARDS, most patients with ARDS require mechanical ventilation. Extensive research has been conducted on the practice of mechanical ventilation in ARDS. At present, no m e t h o d of mechanical ventilation has been shown to be clearly superior in the treatment of ARDS. Nonetheless, in an effort to limit ARDS lung injury, several basic principles of mechanical ventilation are to be considered. 12 Lung injury in ARDS is diffuse yet nonuniform. Ventilation of the ARDS-affected lung will therefore preferentially occur in relatively unaffected alveolar units (Fig 2). 1~ If a relatively high tidal volume is used for volume ventilation, overdistention of relatively unaffected lung units may induce collateral damage. 14Mechanical ventilation of the ARDS patient usually involves some strategy to limit overdistention of relatively unaffected lung units. One of the most straightforward techniques to limit collateral damage is to simply volume ventilate at lower tidal volumes. Traditional postoperative ventilation of the healthy lung is often undertaken at 12 to 15 m L / k g tidal volumes. If
Acute Respiratory Distress Syndrome in Pregnancy
No PEEP
~
Alveolar recruitment
Overdistention
Figure 2. The effect of PEEP on alveolar recruitment, without (A) and with (B) PEEP. Overdistention (C) will result in deleterious effects on intact lung units.
large tidal volume ventilation is used in the face of diffuse ARDS, markedly increased ventilatory pressures will he seen, Use of a lower tidal volu m e (eg, 5 to 8 m L / k g ) may limit p u l m o n a r y barotrauma. 15'16Animal models ~bfARDS suggest that plateau-peak airway pressures of greater than 35 cm H 2 0 appreciably increase barot r a u m a in relatively unaffected alveolar segments. 12'14'1c~8 In summation, one goal of conventional ventilation in ARDS is to limit, if possible, peak-plateau airway pressure to less than 35 cm H20.12 Low tidal volume conventional ventilation may adversely affect the relative contribution that dead space makes in tidal breathing. A lower tidal volume at a given respiratory rate will pro-
323
duce a lower minute volume (respiratory rate • tidal volume). To maintain a given minute volume, respiratory rate must be increased as tidal volume is reduced. At low tidal volumes, a relatively larger portion of a given inspiration involves dead space ventilation. Because dead space ventilation is not effective in gas exchange, low tidal volume breathing becomes progressively less effective in gas exchange. 8 Acute respiratory distress syndrome itself is a circumstance in which dead space ventilation is increased. 9'1~ Low tidal ventilation may therefore significantly exaggerate the already affected dead space-tidal volume relationship of the injured ARDS lung. Pressure-controlled ventilation has b e e n used in an effort to reduce p e a k plateau airway pressure. By ventilating lungs to a given pressure, gas flow, and inspiratory time and rate may be used to affect tidal breathing. Reversal of the n o r m a l 1:1.3 ratio of inspiration to expiration is often a t t e m p t e d in the context of pressure-controlled ventilation. "Inverse ratio pressure controlled ventilation" may allow reduction in peak airway pressure (at the expense of m e a n airway pressure). 19 Although this technique holds m u c h promise, it has not yet b e e n shown to reduce the mortality observed in adult patients with ARDS. 12'2~ Airway pressure release ventilation and high frequency ventilation have also had largely inconclusive results in the t r e a t m e n t of ARDS. In an effort to limit barotrauma, m a n y clinicians elect to modify the "physiological" treatm e n t goals of normal-range arterial blood gases when caring for mechanically ventilated ARDS patients. Permissive h y p e r c a p n e a and the tolerance of relatively low PaO2 levels are used in an effort to limit tidal volume-induced barotrauma, hyperoxia, and the necessity for high levels of PEEP. Once again, these techniques hold p r o m ise, but their impact on survival in ARDS is, as o f yet, unproven, a2 Extracorporal membrane oxygenation (ECMO) was first used in the t r e a t m e n t of ARDS m o r e than 20 years ago. As with the techniques previously mentioned, the promise ECMO holds in ARDS m a n a g e m e n t revolves a r o u n d ECMO's potential ability to limit b a r o t r a u m a through very limited use of the ECMO/ARDS patient's own lungs during the most severe stages of ARDS. In that ECMO is highly successful in children, the National Institutes of Health sponsored
324
James W.. Van Hook
multicenter trials of ECMO in adult patients with ARDS. 22'23 In that outcome was not appreciably different from the conventionally ventilated control group, ECMO was not d e e m e d superior/1'23 Nonetheless, ECMO may have a defined place in the treatment of some patients with ARDS. It is h o p e d that newer trials may identify particular candidates who may benefit from ECMO. Other techniques tried in ARDS include intravenous oxygenation, inhaled nitric oxide, computer-modulated mechanical ventilation, exogenous surfactant administration, high frequency ventilation, and partial liquid ventilation. 21'24'25 Partial liquid ventilation with perfluorochemicals is particularly promising in that it may be both anti-inflammatory and barotrauma-protectire. 26 Trials are currently underway concerning partial liquid ventilation in ARDS.
Anti-inflammatory Therapy As implied earlier in this review, ARDS encompasses the process of diffuse propagated inflammatory injury to the lung. Consequently, several treatment strategies have been investigated to potentially modulate the inflammatory process activated in ARDS. As mentioned previously, inhaled nitric oxide (NO) has been used in the mechanical ventilation of ARDS patient. 25'27 Inhaled NO will decrease pulmonary artery pressure and increase arterial oxygenation by selectively dilating pup monary vessels in ventilated alveolar segments o f the lung. The feasibility of NO ventilation in ARDS was investigated by Rossaint et al in 1993. 25 One unresolved issue with NO administration involves its potential for injury propagation through its function as a free radical. 2s In that NO may both propagate oxidation and, in certain instances, be instrumental in termination of lipid peroxidation chain propagation, the optim u m use of NO as both an aid to mechanical ventilation a n d / o r a mediator of inflammation is unresolved. 2s-31 Anti-inflammatory treatment of ARDS with more clinically available agents has also been investigated. Corticosteroids seem to offer no benefit (and perhaps some harm) to ARDS patients treated with those agents. 32 T h r o u g h inhibition of platelet aggregation, limitation of lysosomal enzyme release, and suppression of polymorphoneutrophil chemotaxis, prostaglandin E1 (PGE~) was thought to be potentially useful in ARDS
propagated inflammatory injury. Unfortunately, Bone e t al failed to show any demonstrable benefit in survival from PGE1 administration in ARDS. 33 Cyclooxygenase inhibitors, such as ibuprofen, display some positive effect on animals with ARDS. Randomized h u m a n trials have shown some improvement in ventilatory support indices, but fail to impart any appreciable survival advantage with their use. 34'35 The antifungal agent ketoconazole has pharmacological activity as an inhibitor of leukotriene and thromboxane synthesis. Although the efficacy of ketoconazole in treatment is unclear, at least one study has shown a reduction of the incidence of ARDS in at-risk patients prospectively treated with ketoconazole, a6 Other agents, such as pentoxifylline, also may reduce the incidence of ARDS in at-risk patients. 28'~7 In summation, various pharmocological agents have been used to attenuate the progression of ARDS. At present, no single agent or treatment has reliably improved outcome in patients with ARDS. It is h o p e d that further research will illuminate effective anti-inflammatory treatment for ARDS.
Management of ARDS in Pregnancy Compared with ARDS m a n a g e m e n t during nonpregnancy, m a n a g e m e n t during pregnancy is simultaneously similar and different. Several issues of ARDS care during pregnancy will be discussed in the following section.
Oxygenation and Acid Base As m e n t i o n e d previously, in an effort to limit pulmonary barotrauma, traditional wisdom in arterial blood gas interpretation has generally been supplanted by a philosophy of nonphysiological tolerance of at least some degree of acidbase abnormalities and relative hypoxemia in adult ARDS management. Permissive hypercapnea, limitation of PEEP (at the expense of PaO2) and low minute volume breathing have all been used. Pregnancy may place some constraints on nonphysiological arterial blood gas goals. As m e n t i o n e d elsewhere in this issue, pregnancy normally induces a state of compensated respiratory alkalosis. Therefore, arterial partial pressure of oxygen (PaCO2), is normally 5 to 10 m m Hg less during pregnancy than it is in n o n p r e g n a n t
Acute Respiratory Distress Syndrome in Pregnancy
subjects. 38 Uteroplacental perfusion has been shown to be reduced in the circumstance of even lower PaCO2. 39 More germane to ARDS treatm e n t in ,pregnancy is the potential for fetal acidbase d e r a n g e m e n t from" the use of permissive hypercapnea (and the concomitant respiratory acidosis) in ARDS ventilator management. Therefore, until more data are available, we generally endeavor to maintain relatively physiological PaCO2 levels during mechanical ventilation of pregnant ARDS patients. The issue of PaO2 is less clear. It is postulated that placental transfer of oxygen is venous oxygen content-mediated. Although maternal arterial oxygen content is not appreciably increased at PaO2 levels above 60 m m Hg (and infinitesimally increased at PaO2 levels greater than 100 m m Hg), maternal venous oxygen content is somewhat increased at higher PaO2 levels. Because elevated venous content could favorably influence placental oxygen delivery, many clinicians think that supranormal PaO2 levels (such as those observed in healthy p r e g n a n t patients receiving supplemental oxygen) might augment transplacental fetal oxygen delivery. However, both the increase in maternal 2,3-diphosphoglycerate and the relatively increased affinity of fetal hemoglobin for oxygen tend to support at least some degree of maternal-fetal tolerance for relative hypoxia. 6'39'4~We therefore think that 60 m m Hg is a reasonable goal in pregnant patients with ARDS. Data from pregnant women studied at high altitude support the concept that fetal oxygen delivery is adequate at PaO2 levels of 60 m m Hg. 41 A final acid-base issue to consider in the care of the critically ill ARDS obstetric patient involves serum HCOs. Because pregnancy is a compensated acid-base state, HCO~ decreases. Consequently, serum-buffering capacity is decreased during pregnancy. Therefore, any intrinsic (disease state-mediated) or iatrogenic inducers of metabolic or respiratory acidosis may potentially be less well-tolerated in pregnancy.
Mechanical Ventilation A complete discussion of mechanical ventilation in pregnancy is beyond the scope of this article. Nonetheless, several important )ssues deserve discussion. The decision to mechanically ventilate a pregnant patient with ARDS should ideally be made in such a way as to (if possible!) allow
325
the elective intubation of the patient. Because pregnant patients usually are relatively young and often otherwise reasonably healthy, they may be able to tolerate periods of high work of breathing spontaneous ventilation somewhat better than the typical intensive care patient with ARDS. Unfortunately, the very tolerance of severe lung disease may predispose the pregnant patient to profound, rapidly progressive respiratory failure once her physiological reserve is expended. Also, the progressively smaller tidal volumes observed in developing increased work of breathing respiratory failure may potentiate atelectasis from the normally diminished functional residual volume observed in pregnancy. Supine positioning further aggravates this process. Finally, arterial blood gas interpretation should be made in the context of what is normal for pregnancy. Ergo, a normal (for n o n p r e g n a n t individuals) PaCO2 may be indicative of ventilatory failure in a pregnant patient. A " n o r m a l " pulseoximetry reading may not become abnormal until after respiratory failure o c c u r s . 42 In any case, careful observation for impending respiratory failure should be part of the care for any unintubated pregnant patient with acute lung injury or ARDS. Little data are available regarding the use of specific techniques o f ventilation in pregnant ARDS patients. At our institution, we routinely administer mechanical ventilation to pregnant patients in a dedicated unit within our labor and delivery area. We generally use conventional volume-cycled mechanical ventilation as our initial modality. When we are unable to maintain PaO2 of at least 60 to 65 m m Hg on 50% or less inspired oxygen, we use PEEP in amounts of up to 15 cm H20. When peak plateau inspiratory pressure is consistently above 35 to 40 c m H 2 O , we use pressure-controlled ventilation. Because pregnant patients with ARDS often have potentially reversible disease processes, they may therefore represent a subgroup of ARDS victims who may benefit from aggressive use of advanced techniques and measures. Individualization of care is key. Fluid Management Two schools of thought exist regarding fluid m a n a g e m e n t in n o n p r e g n a n t patients with ARDS. If considered strictly from a pulmonary standpoint, reduction in lung water and im-
326
James W.. Van Hook
provemenls in gas exchange, compliance, and oxygenation can be accomplished with fluid restriction and relative hypovolemia. However, because many cases of ARDS are associated with multisystem dysfunction or sepsis, body tissue perfusion and collateral organ d a m a g e may occur with hypovolemia or hypoperfusion. Therefore, fluid homeostasis and therapy in ARDS is usually, at best, a compromise between lung water and organ perfusionP '11 Pregnancy, of course, alters this compromise between perfusion and lung water by introducing another organ system, the placenta. Most obstetric providers recognize the limited tolerance of the fetoplacental unit to hypovolemia. Volume homeostasis in the p r e g n a n t individual in effect becomes a three-way compromise involving lung water, maternal perfusion and fetal perfusion, and oxygen delivery. Fetal heart rate monitoring may offer a surprising measure of relative intravascular volume status in the pregnant individual, as Invasive h e m o d y n a m i c monitoring, if used, may allow the optimization of this compromise. O u r developed philosophy has entailed relative fluid restriction provided that fetal tolerance is evident, metabolic acidosis is not present, renal and other organ perfusion is maintained, vasopressors are not required, and hemodynamically influential modes of mechanical ventilation are n o t required. If these conditions cannot be met with relative fluid restriction, empirical volume administration a n d / o r invasive monitoring is usually required.
Sedation/Paralysis/Nutrition Sedation a n d / o r pain relief is usually advisable in the care of intubated patients with ARDS. In addition to providing for patient comforq sedation and pain relief may reduce maternal oxygen consumption and lessen the effects any given m o d e of ventilation may have "on the developm e n t of barotrauma. Nondepolarizing skeletal muscle paralysis (along with sufficient sedation) may be required if advanced modes of ventilation are necessary. Proper monitoring and the recognition of potential complications involved with paralysis are r e c o m m e n d e d if paralysis is used. Because ARDS may require several days (or weeks) of intubated care, nutritional support is very important. If possible, enteral feeding is preferred and may reduce the translocation of gastrointestinal bacteria into the body. Because
of the additional nutritional requirements of pregnancy, indirect calorimetry may be advisable for the long-term monitoring of the enterally or parenterally fed p r e g n a n t patient.
Conclusion ARDS presents a set of unique challenges to the providers faced with a critically ill obstetric patient. Recognition of the special circumstances involved in pregnancy are central to the p r o p e r care of the p r e g n a n t patient with ARDS. As necessary, multidisciplinary care with early referral to an appropriate tertiary care center will optimize the o u t c o m e in this serious disorder. Finally, recognition of the often-reversible nature of some cases of ARDS during pregnancy may foster a clinician's pursuit of advanced therapeutic opportunities.
References 1. Ashbaugh DG, BigelowDB, Petty DB: Acute respiratory distress in adults. Lancet 2:319-323, 1967 2. Taylor RW, Duncan CA: The adult respiratory distress syndrome. Res Medica 1:17-24, 1983 3. Foner BJ, Norwood SH, Taylor RW: The acute respiratory distress syndrome, in CivettaJM, Taylor RW, Kirby RR (eds): Critical Care, ed 3. Philadelphia, PA, Lippincott~Raven, 1997, pp 1825-1840 4. Mahie WC, Barton JR, Sibai BM; Adult respiratory distress syndrome in pregnancy. Am J Obstet Gynecol 167:950-957, 1992 5. Perry KG, Martin RW, Blake PG, et al: Maternal outcome associated with adult respiratory distress syndrome. Am J Obstet Gynecol 174:391, 1996 (abstr) 6. Cunningham FG, MacDonald PC, Gant NF, et ah Williams Obstetrics, ed 20. Stamford, CT, Appleton & Lange, 1997 7. The American-European Consensus Conference on ARDS. AmJ Respir Crit Care Med 149:818-824,1994 8. WestJB:RespiratoryPhysiology-TheEssentials, ed 5. Baltimore, MD, Williams & Wilkins, 1995 9. ShoemakerWC, Appel PL: Pathophysiologyof adult respiratory distress syndromeafter sepsis and surgicaloperations. Crit Care Med 13:166-172, 1985 10. Gattinoni L, Bombino M, Pelosi P, et ah Lung structure and function in different stages of severe adult respiratory distress sYndrome.JAMA271:1772-1779, 1994 11. Gropper MA, Weiner-KronishJP: Acute lung injury and acute respiratorydistress syndrome, in MurrayMJ, Coursin DB, Pearl RG, Prough DS (eds): Critical Care Medicine: Perioperative Management. Philadelphia, PA, Lippincott-Raven, 1997, pp 441451 12. SlutskyAS, Brochard L, Dellinger, et al: ACCPconsensus conference-mechanical ventilation. Chest 104:18331859, 1993
Acute Respiratory Distress Syndrome in Pregnancy
13. Gattino.ni L, Pesenti A, Bombino M, et al: Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure. Anesthesiology 69:824-832, 1988 14. Finger S, Rocker G: Alveolar overdistention is an important mechanism of persisfent lung damage following severe protracted ARDS. Anaesth Intens Care 24:569573, 1996 15. Hickling K: Low mortality associated with low volume pressure limited ventilation with permissive hypercapnea in severe adult respiratory distress. Intensive Care Med 16:372-377, 1990 16. Fu Z, Costello ML, Tsukimoto K, et al: High lungvolume increases stress failure in pulmonary capillaries. J Appl Physiol 73:123-133, 1992 17. ParkerJC, Hernandez LA, Peevy KJ: Mechanisms ofventilatol~induced lung injury. Crit Care Med 21:131-143; 1993 18. Dryfuss D, Basset G, Soler P, et ah Intermittent positivepressure hyperventilation with high inflation pressuresproduces pulmonary microvascular injury in rats. Am Rev Respir Dis 132:880-884, 1985 19. Lain DC, DiBenedetto R, Morris SL, et al: Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation. Chest 95:1081-1088, 1989 20. Morris AH, Wallace CJ, Clemmer TP, et al: Final report: Computerized protocol controlled clinical trial of new therapy which includes ECCO2-R for ARDS. Am Rev Respir Dis 142(Part 2):A184 (absrr) 21. Morris AH: Adult respirator5, distress syndrome and new modes of mechanical ventilation: reducing the complications of high volume and high pressure. New Horizons 2:19-33, 1994 22. Anderson HL III, Bartlett RH: Extracorporeal and intravascular gas exchange devices, in Ayres SM, Gsenvik A, Holbrook PR, Shoemaker WC (eds): Textbook of Critical Care, ed 3. Philadelphia, PA, WB Saunders, 1995, pp 943-951 23. Morris AH, Wallace CJ, Menlove RL, et al: Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 149:295-305, 1994 24. Conrad SA, EggerstedtJM, Morris VF, et al: Prolonged intracorporeal support of gas exchange with an intravenacaval oxygenator. Chest 103:158-161, 1993 25. Rossaint R, Falke KJ, Lopez F, et ah Inhaled nitric oxide for the adult respiratory distress synttrome. N EnglJ Med 328:339-405, 1993 26. Hirschl RB, Parent A, Tooley R, et al: Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure. Ann Surg 221:7988, 1995 27. Krafft P, Fridrich P, Fitzgerald RD, et ah Effectiveness of
327
nitric oxide inhalation in septic ARDS. Chest I09:486493, 1996 28. Louie S, Halliwell B, Cross CE: Adult respiratory distress syndrome: A radical perspective. Adv Pharmacol 38:457490, 1997 29. Darley-Usmar V, Wiseman H, Halliwell B: Nitric oxide and oxygen radicals: A question of balance. FEBS Lett 369:131-135, 1995 30. Wink DA, Cook JA, Pacelli R, et ah Nitric oxide (NO) protects against cellular damage by reactive oxygen species. Toxicol Lett 82:221-226, 1995 31. Moncada S, Higgs EA: Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEBJ 9:13191330, 1995 32. Bernard GR, LuceJM, Sprung CL, et al: High dose corticosteroids in patients with adult respiratory distress syndrome. N EnglJ Med 317:1565-1570, 1987 33. Bone RC, Slotman G, Maunder R, et al: Randomized double-blind multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Chest 96:114-119, 1989 34. Haupt MT, Jastremski MS, Clemmer TP, et al: The ibuprofen study group: effect of ibuprofen in patients with severe sepsis. A randomized double-blind, multicenter srudy. Crit Care Med 19:1339-1347, 1991 35. Bernard GR, Wheeler AP, Russell JA, et al: The effects of ibuprofen on the physiology and survival of patients with sepsis. N EnglJ Med 336:912-918, 1997 36. Yu M, Tomasa G: A double-blind, prospective, randomized trial of ketoconazole, a thromboxane synthetase inhibitor, in the prophylaxis of the adult respiratory distress syndrome. Crit Care Med 21:1635-1642, 1993 37. Montravers P, Fagon ]Y, Gilbert C, et al: Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory distress syndrome. Chest 103:1017-1022, 1993 38. Van HookJW, Owens TM: Care of critically ill obstetric patients, in Murray MJ, Coursin DB, Pearl RG, Prough DS (eds): Critical Care Medicine: Perioperative Management. Philadelphia, PA, Lippincott-Raven, 1997, pp 733743 39. Levinson G, Shnider SM, DeLorimier AA, et al: Effects of maternal hyperventilation on uterine blood flow and fetal oxygenation and acid-base status. AnesthesioloN~ 40:340-347, 1974 40. Rorth M, Brahe NE: 2,3-Diphosphoglycerate and creatine in the red cell during human pregnancy. Scand J Clin Lab Invest 28:271-276, 1971 41. Sobrevilla LA, Cassinelli MT, Carcelen A, et al: Human fetal and maternal oxygen tension and acid-base status during delivery at high altitude. Am ] O b s t e t Gynecol 111:1111-1118, 1971 42. Van HookJW, Harvey CJ, Anderson GD: Effect of pregnancy on maternal oxygen saturation values: Use of reflectance pulse oximetry during pregnancy. South Med J 89:1188-1192, 1996