Acute Renal Failure and Mechanical Ventilation: Reality or Myth?

Acute renal failure (ARF) is a common complication in critically ill patients. In a 5-year analysis of incidence and mortality published in 2002, Pruchnicki and Dasta¹ estimated that it occurs in up to 25% of all patients admitted to the hospital with a critical illness. In a more recent multicenter, multinational analysis² of almost 30000 intensive care unit (ICU) admissions in 54 study centers in 23 countries, ARF developed during the hospital stay in 5.7% of all the patients. Of those patients, approximately 60% died, with a higher prevalence among patients receiving renal replacement therapy. Although dialysis techniques have markedly improved since the 1980s, resulting in improved outcomes, ARF remains an independent predictor of hospital mortality in critically ill patients.^2,3 In fact, the process of or the comorbid conditions associated with the development of ARF appear to contribute to overall mortality. Thus, patients admitted to the ICU who subsequently have renal failure seem to have worse outcomes than do patients admitted with preexisting acute renal failure.⁴

Development of ARF in patients who are not critically ill is associated with significant increases in mortality and in hospital costs due to longer lengths of stay and treatments related to ARF. When ARF develops in patients with critical illness, the costs and adverse outcomes increase even more dramatically.^5–7 Liangos et al⁶ used data from the 2001 National Hospital Discharge Survey to explore the relationship between ARF and hospital length of stay and mortality. Patients with ARF had a 2-day increase in length of stay, a higher mortality rate, and an adjusted odds ratio of 2.0 for discharge to short- or long-term care facilities. In a smaller study, Vieira et al⁸ found a link between acute kidney injury and unsuccessful weaning from mechanical ventilation resulting in increases in duration of mechanical ventilation, lengths of stay, and ICU mortality.

Although common, perhaps ARF is not inevitable. Evidence suggests a link between positive-pressure ventilation and ARF.⁹ In this article, I briefly review renal anatomy and physiology, acute renal failure, the systemic effects of mechanical ventilation, and how attempts to salvage respiratory function may actually compromise other end-organ function.

Renal Anatomy and Physiology

Although their primary function is to filter and excrete wastes and toxins, the kidneys also regulate fluids, electrolytes, and acid-base balance. They receive 20% to 25% of the entire cardiac output. More than half of the blood flow through the kidney consists of plasma. Of the renal plasma flow, approximately 20% is filtered through the glomeruli (the glomerular filtration rate [GFR] is an estimate of the amount of blood that passes through each minute). The remaining plasma flows through efferent arterioles.^10,11 The amount that flows through these arterioles depends directly on renal blood flow (RBF), and any alterations in blood flow will alter the GFR.

Each kidney receives its blood supply through a single renal artery that divides into different branches, which divide even further to provide blood to all of the nephrons. The nephrons are unique because they have 2 capillary systems: the high-pressure glomeruli and the low-pressure reabsorptive peritubular capillary network. Each glomerulus is flanked by afferent and efferent arterioles (Figures 1 and 2), which selectively constrict or dilate to regulate the pressure within the glomeruli.¹¹ Blood passes through the glomerulus and into structures called Bowman’s capsules (Figure 2).

View larger version (62K): [in this window] [in a new window] Figure 1 The nephron.

View larger version (64K): [in this window] [in a new window] Figure 2 Bowman’s capsule and glomerular apparatus.

The glomerular capillary membrane has 3 layers: the inner capillary endothelium, the basement membrane, and the outer capillary epithelium^10,11 (Figure 2). The glomerular filtrate passes through all 3 layers, through the nephrons, and into the proximal tubule. From there, the filtrate continues to travel through the loops of Henle and into distal tubules before passing on to the collecting ducts (Figure 1). At each step, fluids, ions, and electrolytes are exchanged.

Of note, nephrons are the functional units of the kidney and consist of the cortical nephrons (85%) and juxtamedullary nephrons (15%).¹³ The primary functions of cortical nephrons are excretory and regulatory, whereas the primary function of juxtamedullary nephrons is urine concentration and dilution through a countercurrent mechanism as the urine travels through the long loops of Henle.¹³ Although the cortical nephrons have loops of Henle, the loops are of various lengths and do not include the thin ascending loop that is present in the juxtamedullary nephrons. The long, ascending loops and the vasa recta are responsible for urine concentration and dilution.¹³ (The vasa recta are vessels that closely follow the loops of Henle and with them, through a countercurrent mechanism, play an important role in urine concentration and dilution.¹³)

Autoregulation maintains the pressure within Bowman’s capsules at a reasonably constant rate of 80 to 180 mm Hg.¹⁰ At higher pressures, the afferent arterioles constrict, preventing increased glomerular blood flow. At lower pressures, the arterioles dilate, increasing glomerular blood flow. This process maintains a fairly constant filtration and excretion of fluids and solutes.¹⁰ The reflexive relationship between RBF and arterial pressure is maintained by neural regulation. With decreased systemic arterial pressures, sympathetic nerve activity signals the baroreceptors in the aortic arch. Decreased pressures cause renal arteriolar vasoconstriction, which decreases filtration and excretion. This mechanism increases intravascular volume and thus increases blood pressure. Conversely, increased systemic arterial pressure leads to renal arteriolar vasodilatation and increased filtration and excretion of fluids.^10,11

Acute Renal Failure

ARF is defined as a sudden reduction (from hours to days) in GFR¹⁴ and is associated with an accumulation of nitrogenous wastes and alterations in fluid, electrolyte, and acid-base balance.^15–17 ARF may be associated with decreased urine output and is often manifested by an output of less than 30 mL/h or less than 400 mL/d.¹⁵ Fortunately, ARF can usually be reversed if detected early.¹⁷ ARF is classified as prerenal, intrarenal, or postrenal (Table 1). It has many causes, which can include conditions inherent to a patient’s disease process, such as infections, vascular obstructions, and severe hypotension. The cause can also be iatrogenic, such as administration of contrast medium or medications.^15,16

View this table: [in this window] [in a new window] Table 1 Major causes of acute renal failurea

Prerenal failure, the most common cause of ARF,¹⁴ is caused by a mild to moderate decrease in RBF,¹⁴ which decreases glomerular filtration.¹⁵ Hypovolemia, whether relative (eg, through third spacing) or absolute (eg, through blood loss), or low cardiac output decreases renal perfusion. The renal vasoconstriction caused by decreased cardiac output ultimately causes renal hypoperfusion with a general impairment of the renal regulatory response.^15,16,18 However, renal damage generally does not occur, and if it does, it can usually be quickly reversed if treated promptly.¹⁴

Intrarenal failure is categorized according to the location where it occurs, such as tubular, interstitial, or glomerular.¹⁶ It is often caused by the same processes that cause prerenal failure, such as ischemia, which may be caused by severe hypotension due to hypovolemia, or nephrotoxins.^9,14,15 Acute tubular necrosis is common and often occurs after surgery. Different parts of the kidney are more sensitive to the effects of ischemic injury than are others. For example, the proximal tubules depend on mitochondrial respiration for energy,⁹ and any interruption in perfusion decreases oxygen delivery. Intrarenal ischemia generates release of oxygen free radicals and inflammatory mediators, such as tumor necrosis factor (TNF-), which cause marked tissue injury.⁹ The renal medulla is more susceptible because it becomes more hypoxic than the renal cortex does with decreased blood flow.^9,15

Although generally rare, postrenal failure is generally characterized by blockage of all urine flow by obstruction of the ureters, bladder neck, or urethra.^14,16 The obstruction leads to a retrograde urinary flow into the renal structures because urine cannot be expelled. Over hours to days, renal structures gradually distend, leading to a decrease in the overall GFR.¹⁴

Systemic Effects of Mechanical Ventilation

Recent evidence suggests that mechanical ventilation may contribute to the pathogenesis of ARF, and several mechanisms have been proposed to explain the association^9,19 (Figure 3). One possible mechanism is compromise of RBF by permissive hypercapnia or permissive hypoxemia. Another possibility is a pulmonary inflammatory reaction in response to biotrauma, with the release of inflammatory mediators and the induction of a systemic inflammatory reaction.^9,20

View larger version (36K): [in this window] [in a new window] Figure 3 Mechanisms associated with mechanical ventilation that may lead to acute renal failure.

Hypercapnia and Hypoxemia
Mechanical ventilation, through the manipulation of PaCO₂ and PaO₂, may affect vascular dynamics via activation or inactivation of vasoactive factors such as nitric oxide, angiotensin II, endothelin, and bradykinin.⁹ Hypercapnia is inversely correlated with RBF and causes renal constriction by direct and indirect mechanisms.⁹

The direct mechanisms include activation of the sympathetic nervous system by release of norepinephrine. The increased sympathetic activity reduces RBF and GFR and contributes to a nonosmotic release of vasopressin.⁹

The indirect mechanism is a decrease in systemic vascular resistance due to systemic vasodilatation. The decrease leads to further release of norepinephrine and stimulation of the renin-angiotensin-aldosterone system, causing decreased RBF²¹ (Figure 4). These hypercapnic effects occur independently of PaO₂ and determine the renovascular response to changes in arterial blood gas parameters.⁹

View larger version (37K): [in this window] [in a new window] Figure 4 Renin-angiotensin-aldosterone system.

Severe hypoxemia (PaO₂ <40> and increased renal vascular resistance, which leads to renal hypoperfusion, decreased GFR, and functional renal insufficiency. The effects of moderate hypoxemia on renal hemodynamics are less understood. One suggestion is that mild hypoxemia, without simultaneous hypercapnia, may not markedly affect renal hemodynamics.⁹ Another suggestion is that acute normocapnic hypoxemia increases renal vascular resistance, leading to renal hypoperfusion and decreased GFR.⁹

Cardiopulmonary Dynamics
The proximity of the pulmonary and cardiac vasculature within the thorax and the dynamic mechanical pressure functions ensure that any changes in intrathoracic pressures affect cardiac function, even in patients not receiving mechanical ventilation.²² In healthy individuals, cardiovascular effects appear to be directly related to the amount of pressure change within the thorax.²² Positive-pressure mechanical ventilation markedly affects cardiac performance by acting on preload and cardiac output.^23,24 Intrathoracic pressures influence the epicardium and affect the function and volume of both ventricles. Decreased intrathoracic pressures usually cause decreased transmural pressures (difference between intraventricular and pleural pressures^25,26), and the decreases in transmural pressure assist in ventricular filling.²² Thus, if positive pressure increases pleural pressure, transmural pressure and afterload are decreased.^22,26 Positive intrathoracic pressure impairs venous return, decreases ventricular distensibility,²⁴ and causes decreased ventricular filling. The decreased venous return leads to a decrease in right ventricular preload, which through sustained pressure changes in the cardiopulmonary vasculature leads to a sustained, decreased left ventricular afterload.^22,27 Ultimately, decreased left ventricular preload decreases left ventricular afterload. These changes reduce cardiac output because although left ventricular afterload is reduced, the decreased left ventricular filling has a greater effect on cardiac output.²⁸ In patients with pulmonary disease, this effect is exacerbated. For example, in patients with reduced lung volumes, as might occur in obstructive disorders or decreased functional residual capacity (eg, supine positioning, anesthesia), resistance in the extra-alveolar pulmonary vessels can occur.²²

Positive end-expiratory pressure (PEEP) may reduce cardiac output by causing a further increase in intrathoracic pressures, which compresses the pulmonary vasculature.²⁹ This change increases right ventricular afterload, leading to a decrease in emptying and ultimately a decrease in left ventricular preload.^29–32 Left ventricular distensibility also decreases, with an associated decrease in left ventricular function, especially with PEEP greater than 15 cm H₂O. The decrease in left ventricular function causes a decrease in venous return to the right side of the heart and an increase in pulmonary artery pressures.^30–32 In studies in animals, the effects of PEEP on hemodynamic parameters have varied. In one study, PEEP up to 14 cm H₂O did not adversely affect ejection fraction or left ventricular end-diastolic volume but at levels greater than 21 cm H₂O had marked effects on these 2 parameters.³³ However, in other studies, PEEP at 10 to 14 cm H₂O, markedly affected cardiac index.³³ Harmful effects of PEEP may be more important with patients with additional comorbid conditions such as may be found in a systemic inflammatory response. However, euvolemic patients without additional comorbid conditions are considered to be at less risk³⁴ because blood vessels in patients with adequate volume are less likely to collapse.²⁶

Because the kidneys receive 20% to 25% of cardiac output, any decrease in cardiac output caused by PEEP affects RBF.⁹ RBF is primarily affected by PEEP because of sympathetic activation related to increased plasma renin activity.²⁹ Results of other studies^9,35 have also suggested that although total RBF is relatively unchanged, blood flow is redistributed from the cortical to the juxtamedullary nephrons. This redistribution would be associated with decreased urine output, decreased creatinine clearance, and an increased fractional resorption of sodium³⁵ (Figure 4).

PEEP further affects the hormonal and sympathetic pathways. The effect is due to an increase in sympathetic tone, which is caused by increased plasma renin activity and decreases GFR because of decreased blood flow. PEEP has a transient effect on aortic blood pressure, and this effect reflexively activates the sympathetic nervous system through aortic and (sino)carotid baroreceptors. Changing renal function then slowly affects intravascular volume.⁹

Ventilator-Induced Lung Injury and Cytokine Response
In addition to altering RBF, mechanical ventilation alters renal function through the release of proinflammatory cytokines. Researchers^20,36–38 have shown a link between mechanical forces in diseased lungs and the resulting inflammation and/or rupture of alveoli, which leads to the release of proinflammatory cytokines. Diseased lungs such as those that occur in various respiratory disease syndromes have smaller capacities than do healthy lungs, a characteristic that can make the diseased organs more susceptible to mechanical injury through mechanical ventilation.³⁹ As alveoli repeatedly open and close, more injury occurs through shear stresses.⁴⁰ This situation can lead to regional lung injuries, a process called recruitment/derecruitment.⁴¹ Because of the collapsed areas (as may occur in atelectasis), smaller areas are available for mechanical ventilation. This decrease leads to excessive dilatation of the remaining areas of normally aerated lung tissue that are naturally more compliant (nonatelectatic).^41,42 In fact, the initial trigger of ventilator-induced lung injury (VILI) is mechanical injury, not inflammation.⁴³ Therefore, if mechanical injury is reduced, the risk for VILI is reduced.

Mechanical forces affect fibers of the extracellular matrix and alveolar cells, producing alveolar cell strain.³⁹ The fibers of the extracellular matrix system contain collagen and elastin that connect the endothelium and epithelium. The elastin is springlike and allows the lungs to return to their resting state during exhalation. If the extracellular matrix fiber system is overdistended through high-volume or high-pressure ventilation, the fibers stretch and cannot recoil fully. The collagen is fairly nonelastic and acts as a stop-length fiber.³⁹ Its ability to distend is finite, and if overdistended, it can rupture, just as a rubber band does that is stretched too far (Figure 5).

View larger version (29K): [in this window] [in a new window] Figure 5 Stretch and rupture of fibers in the extracellular matrix.

Three-quarters of all lung cells (by volume) are located in gas-exchange regions. Type II epithelial cells (surfactant) are located in alveolar corners. Type I epithelial cells, which account for approximately 90% of the alveolar surface, are flat and wide. A single type I epithelial cell may have up to 4 endothelial cells embedded in it, in a sandwich-like manner.³⁹ In most alveolar structures, type I epithelial cells share a common basal membrane with endothelial cells (Figures 6 and 7). This characteristic suggests that the cells are mechanically coupled. With its associated fibroblasts, the fiber system and myosin and actin filaments contribute to mechanical support and are located in the basal membrane (extracellular matrix). The epithelial and endothelial cells are anchored to the basal membrane via integrins.³⁹

View larger version (82K): [in this window] [in a new window] Figure 6 Air-blood barrier.

View larger version (93K): [in this window] [in a new window] Figure 7 Alveolar cell walls. Only 2 thin cells, the alveolar epithelial cell and the capillary endothelial cell, separate the alveolar airspace from fluid in the capillary.

All of the anchored cells accommodate as stretch and strain are applied, but only to a point.³⁹ The cells react to strain-induced deformation by recruiting intracellular lipids to the cell surface to reinforce or seal the plasma membranes.³⁹ This process causes an upregulation of inflammatory cytokines. As the alveolar cell surfaces increase because of the additional stretch, the progressive strain causes macrophages to produce interleukin 8 (IL-8),⁴³ which recruits neutrophils to the site, and metalloproteins, which remodel the extracellular matrix.³⁹ In an animal model, a 50% surface strain was equivalent to a total volume change greater than total lung capacity, and 70% of the cells died.³⁹ Ultimately, neutrophil recruitment leads to inflammation in proportion to strain.³⁹ Damage is increased by the duration of the injury, the amplitude of the pressures, and frequency of the injury.

As strain increases in the pulmonary capillaries, the capillary meshwork begins to flatten, whereas the corner vessels maintain or increase patency.³⁹ The increased resistance to blood flow causes an increase in pulmonary artery pressures and an increase in filtration rate in excess of the increased lymph flow; the result is accumulation of fluid in the interstitial spaces. Pulmonary edema impairs gas exchange and promotes formation of hyaline membranes and infiltration of neutrophils. Furthermore, the increased permeability of the capillary network causes increased hydrostatic pressure, and possibly an increase in neutrophil-induced inflammation.

The increased strain induces bacterial translocation within the alveolar system⁴⁶ (Figure 5). Repeated opening and closing of distal alveoli may cause shearing of epithelial layers, which are extremely thin^44,45 (Figures 6 and 7). With high-volume ventilation, surfactant is then inactivated, primarily because of atelectasis. Subsequently, epithelial desquamation may cause easier bacterial access to the bloodstream. The effect of higher peak inspiratory pressure without PEEP may cause intra-alveolar edema as alveolar septal walls thicken, proteinaceous fluid accumulates, and neutrophils infiltrate.⁴³

Studies^38,43 in animal models in recent years also showed that high-tidal-volume ventilation coupled with low PEEP created a higher propensity for bacterial translocation into the bloodstream. However, PEEP can stabilize alveoli and seems to reduce the risk of microatelectasis.⁴³

The ultrastructural changes to lung parenchyma include damage to endothelial and epithelial cells.^46,47 Damaged endothelium then releases inflammatory mediators. The mediators amplify endothelial injury directly or indirectly by recruiting inflammatory cells into the vascular, interstitial, and alveolar spaces. The mediators released, such as TNF- and -thrombin, activate protein kinase C–dependent signaling pathways. This activation of protein kinase C isoforms causes endothelial cytoskeletal elements to contract, enhancing barrier dysfunction.

Some of the cytokines (eg, angiotensins, bradykinin, -thrombin, thromboxane, prostacyclin, and endothelin) have important vasomotor effects^48–53 (Table 2). Metabolism may be impaired by endothelial cell damage, which may lead to adverse effects on interstitial fluid fluctuations.⁴⁷ These altered levels of endothelium-derived vasoactive mediators contribute to microcirculatory dysfunction, including release of reactive nitrogen and oxygen species, and post-capillary resistance may be increased through microcirculatory dysfunction. As the capillary pressures increase, pulmonary edema worsens, impairing the bactericidal activity of alveolar macrophages.^38,46,47

View this table: [in this window] [in a new window] Table 2 Effects of cytokines and mediators

Lung injury caused by release of inflammatory mediators further reduces the caliber of small airways. The associated increase in circulating levels of thromboxane A₂ and serotonin are linked to increases in pulmonary artery pressure. The cellular particulate material and debris and the accumulating perivascular edema cause additional obstruction that impairs cardiac output. These alterations in the pulmonary circuit also alter the compensatory mechanism of pulmonary hypoxic vasoconstriction.⁴²

Mechanical ventilation has a major effect on inflammatory cells and soluble mediators in lungs.³⁶ Several primary cytokines are released through the injury and inflammatory process. They include IL-8,⁹ IL-6,54,55 and TNF-.9,54 These promote glomerular and tubulointerstitial sequestration of neutrophils, upregulation of leukocyte adhesion molecules, and a decrease in filtration fraction associated with alterations in vascular tone^9,54 (Table 2).

Increases in tidal volume are associated with increases in pulmonary, hepatic, and renal levels of IL-6, which correlate with development of ARF.⁹ In addition, release of soluble Fas ligand (sFasL), the ligand for the receptor Fas, causes apoptosis (programmed cell death) of renal epithelial cells and leads to increased levels of biochemical markers indicative of renal dysfunction. The Fas-FasL system induces apoptosis of glomerular cells.⁹ Apoptosis in ARF is due to receptor-mediated activators such as TNF and the Fas-FasL system.⁹ Cytotoxic events, such as ischemia, hypoxia, and anoxia, as well as oxidant injuries and nitric oxide, also lead to apoptosis.⁵⁶ Tremblay and Slutsky³⁸ reported a relationship between various ventilatory modes and subsequent effects on end organs that included increased apoptosis of cells in the kidney and small intestine and changes in host immunity and susceptibility to infection.

Areas for Further Evaluation

Lung-protective mechanical ventilation techniques are still under investigation. These investigations should include determining the optimal combination of PEEP and tidal volume. Other areas to examine are different types of ventilation, such as airway pressure release ventilation (APRV) and high-frequency oscillatory ventilation (HFOV). In addition, conventional ventilation techniques should be reevaluated. Furthermore, nurses should consider the consequences of temporary cessation of ventilatory support and how cessation may or may not cause lung injury. Another area of interest is how nutrition can affect the inflammatory process in critically ill patients receiving mechanical ventilation. All of these areas are important because potentially preventable lung injury caused by mechanical ventilation may have deleterious effects on renal function.

Lung-Protective Ventilation
Efforts to decrease the risk of renal failure induced by mechanical ventilation must include further research in lung-protective ventilation strategies, including judicious application of PEEP,⁵⁷ which in rat models can delay VILI. Because PEEP reduces the pressures required to ventilate lungs, it may be more important than tidal volume in preventing lung injury. The reduction in pressure delays overdistention of the lungs, reduces the mechanical energy load, and ultimately stabilizes damaged alveoli.⁴⁷ Although much research in this area has been done, information is still needed on what constitutes optimal PEEP.

Optimizing Fraction of Inspired Oxygen
Another way to decrease lung injury is to reduce pulmonary inflammation. Maintaining the fraction of inspired oxygen at less than 0.60 may reduce injury caused by oxygen because a high fraction of inspired oxygen causes formation of cytotoxic oxygen free radicals.^24,54 Of equal interest is the phenomenon of absorption atelectasis, in which well-ventilated alveoli empty their oxygen across the concentration gradient and increase the possibility of their collapse.^24,58 The process is exacerbated by nitrogen washout. Breathed air is a combination of multiple gases, of which nitrogen is the major component. The combination of gases is inhaled into the alveoli, where the gases either are absorbed into the plasma or remain in the alveoli. Nitrogen is not particularly soluble in the plasma; therefore, larger concentrations remain in the alveoli, helping the alveoli maintain their structure. If the nitrogen in the alveoli is replaced by other gases, such as excess amounts of highly diffusible oxygen, the alveoli lose much of their ability to retain their open structure.⁵⁹

Tidal Volume Control
Optimizing tidal volume reduces the risk of lung overinflation. The Acute Respiratory Distress Syndrome Network⁶⁰ recommends maintaining a tidal volume of 6 mL/kg, and plateau pressures less than 30 cm H₂O reduce barotrauma and decrease the release of inflammatory mediators. However, additional research⁴³ has suggested that compared with low tidal volumes coupled with high PEEP, which decrease alveolar instability, low tidal volumes coupled with low PEEP may actually be injurious, causing increased release of IL-8. Although mechanical injury may be reduced, optimal tidal volumes have not yet been determined.

Airway Pressure Release Ventilation
APRV does not add tidal volume ventilation to baseline airway pressures.⁶¹ Instead it decreases airway pressure to less than baseline pressure to augment ventilation.³⁴ This augmentation allows patients to breathe spontaneously and releases airway pressure from an elevated baseline value to stimulate expiration. This elevated baseline improves oxygenation while timed airway pressure release aids in carbon dioxide removal. The advantages of this ventilation mode include decreased lung injuries because of lower peak pressures. Pressure limits also eliminate or reduce alveolar overdistention and high-volume lung injury. Maintaining low airway pressure limits lung injury by decreasing repetitious alveolar opening. Because APRV does not increase intrathoracic pressures, venous return is not compromised. This situation leads to an improved cardiac output because as patients breathe spontaneously, associated decreases in intrathoracic pressures facilitate venous return.³⁴ Disadvantages of APRV include permissive hypercapnia,⁶¹ which can be inversely correlated with RBF and can cause renal constriction.⁹

High-Frequency Oscillatory Ventilation
Use of HFOV has been traditionally reserved for neonates and children.^40,62 In studies in animals, tracheal aspirates had lower levels of IL-6, IL-8, TNF-, and other mediators with HFOV than with standard positive-pressure ventilation strategies. HFOV is also being evaluated as a treatment for adults with lung injuries.⁶³ Studies^41,64 have shown that HFOV can provide adequate gas exchange with small tidal volumes and high end-expiratory pressures without producing alveolar overdistention. Decreased alveolar distention should result in decreased VILI, which in turn may lead to further reduction in alveolar inflammatory processes due to mechanical injury. However, potential complications associated with HFOV could outweigh the benefits. In a study of adults with acute respiratory distress syndrome, Chan et al⁶⁴ found that central venous pressure and pulmonary artery occlusion pressures increased, and clinically insignificant decreases in cardiac output and some decreases in stroke volume index and end-systolic and diastolic area indexes occurred. In a study in pigs with normal lungs, Roosens et al⁶⁵ found that HFOV was safe and effective but did not improve mortality rates and in fact greatly elevated intrathoracic pressures. Although this method of ventilation provides valuable lung protection and may prevent VILI, more research is needed to discover how significant the changed hemodynamic parameters affect renal function.

Traditional Mechanical Ventilation
Some of the more traditional strategies to reduce the impact of mechanical ventilation on cardiac output in patients with reduced lung volume include assisted, non-invasive ventilation modes such as continuous positive airway pressure, bilevel positive airway pressure, and pressure-support ventilation. These ventilation methods help recruit alveoli while reducing adverse cardiovascular effects, although more research is needed in this area.²²

Suctioning Techniques
Suctioning in patients receiving mechanical ventilation needs to be further examined. PEEP can impair suctioning because of the pressure gradients between the suction catheter tip, the end of the endotracheal tube, and the alveoli. The positive pressure that is blown through the end of the endotracheal tube maintains PEEP within the alveoli despite the negative pressure in the suction catheter created during closed-system suctioning. This positive pressure forces the secretions to flow distally, away from the suction catheter⁶⁶ and has the effect of layering the secretions around the alveolar walls. In the past, nurses attempted to overcome the layering effect by instilling normal saline into the endotracheal tube, a practice that is now considered unhelpful and possibly harmful.^67,68 With open-system suctioning methods, such as stopping positive-pressure ventilation during the suctioning, the pressure gradient is zero and the catheters can easily remove available secretions.^66,69 However, stopping PEEP, for even short periods, facilitates rapid alveolar derecruitment³⁹ and requires higher pressures after the intervention to recruit lost alveoli. These higher pressures increase the risk of creating higher intrapulmonary stresses and often lead to additional stress-induced lung injury. It may take several hours before the collapsed alveoli are recruited again.⁴⁷

Nutrition
New enteral nutrition formulas can lead to improved mortality and morbidity in critically ill patients receiving mechanical ventilation.^70,71 These low-carbohydrate, high-fat formulations are enriched in antioxidants, eicosapentaenoic acid, and -linolenic acid. They can control the development of proinflammatory mediators.^20,70,71 Interestingly, compared with patients who received traditional enteral feedings, patients who received these special formulations had lower total neutrophil counts, had decreased alveolar levels of IL-6 and IL-8, were weaned from mechanical ventilation at a much higher rate, and had less end-organ failure.^20,70

Conclusion

No consensus exists that positive-pressure ventilation impairs renal function, although evidence that it does is mounting. Nurses who care for patients receiving mechanical ventilation must recognize the possible renal consequences of this pulmonary intervention. Astute nursing assessments of pulmonary and renal function are required.

Additional nursing research is needed to examine the effects of different suctioning techniques on pulmonary function. What is the impact of intermittent cessation of positive pressure on overall outcomes? In addition, could the value of being able to transport patients for diagnostic purposes be balanced, or overshadowed, by the possible harm of cessation of positive-pressure ventilation to some patients’ fragile pulmonary condition? What could be considered optimal combinations of PEEP and tidal volume for different conditions? A particularly interesting topic for further research is the potentially adverse renal effects of treating patients with vasopressin and norepinephrine for hypotension. Are the effects of treatment the same as those of the endogenous release of those substances? Could this treatment lead to activation of the sympathetic nervous system, thus decreasing RBF and GFR? Health care providers should be aware that treatments that benefit one organ system may adversely affect another. Patients are not exclusively a respiratory system, or a renal system, or a hepatic system, or any other specific organ system. They are an integrative whole and must be treated as that whole, with the realization that any intervention that affects one part of a patient may cause unexpected—and unwelcome—results in another body system.²⁷

PRIME POINTS

• What changes associated with mechanical ventilation can acute renal failure be linked to?
  
• How does pulmonary inflammation and/or rupture of alveoli affect renal function?
  
• Research is needed on lung-protective ventilation strategies, including judicious use of PEEP, optimal fraction of inspired oxygen, tidal volume control, airway pressure release ventilation, high-frequency oscillatory ventilation, and traditional mechanical ventilation.
  

Acknowledgments

Thanks to Mark Yerrington, visual information specialist at William Beaumont Army Medical Center, for his creative assistance with the figures. The opinions or assertions contained herein are the private views of the author and should not be construed as official or as reflecting the views of the US Army Medical Department, Department of the Army, or the Department of Defense. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army or Department of Defense endorsement or approval of such products or services of these organizations.

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