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Moving Points in Nephrology |
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois
Address correspondence to: Dr. Patrick T. Murray, Section of Nephrology, MC 5100, Room-511, University of Chicago Hospitals, 5841 South Maryland Avenue, Chicago, IL 60637. Phone: 773-834-0374; Fax: 773-702-5818; E-mail: pmurray{at}medicine.bsd.uchicago.edu
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Introduction |
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 Top Introduction Renal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Renal Effects of ALI and Mechanical Ventilation |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Effects of Mechanical Ventilation and ALI on Renal Function |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Neurohormonal Effects of PPV
PPV has been shown to alter a variety of neurohormonal systems, including sympathetic outflow, the renin-angiotensin axis, nonosmotic vasopressin (antidiuretic hormone [ADH]) release and atrial natriuretic peptide (ANP) production. The end result of all of these neurohormonal pathways is diminished renal blood flow, decreased GFR, and fluid retention (salt and water) with oliguria. Despite conflicting data, there is some evidence that fluid retention is caused by PPV-induced production of vasoactive substances. These mediators shift intrarenal blood flow from the cortex to the medulla, resulting in greater fluid retention at any level of renal perfusion (10,17,18).
ADH release in the setting of PPV is likely multifactorial. While some evidence suggests that decreased atrial stretch due to the absolute or relative intravascular volume depletion associated with mechanical ventilation plays a role in the increased ADH secretion (19), it is clear that there are more factors at play (20). Several experimental denervation procedures (cervical, carotid sinus) in animals have blunted the ADH response, but none has been able to abolish it (20,21). Taken together with evidence that an increase in urine osmolarity is not commonly found as a direct effect of PPV, this suggests that ADH release is not the primary mechanism responsible for the decrease in urine output during PPV.
It should come as no surprise that the renin-angiotensin-aldosterone axis is affected by PPV. PPV has been shown to increase renin activity in both animal models and humans (9,21,22). Animal denervation studies have shown that increased sympathetic flow indirectly leads to the increase in renin activity (20). Thus, PPV leads to increased sympathetic tone, secondary activation of the renin-angiotensin axis, and decreased renal plasma flow, GFR, and urine output. Of course, downstream stimulation of aldosterone production is among the salt-retaining effects of PPV. The limited studies investigating catecholamine levels and PPV have not provided a clear correlation between mechanical ventilation and hormone concentrations (23).
Suppression of ANP release has been proposed as a source of the decreased urine volume and sodium content associated with PPV. Using a canine model, Ramamoorthy et al. showed that plasma ANP levels correlated with right atrial filling pressures and decreased with the initiation of PPV (P < 0.05) (24). While some animal and human studies have supported these data, other human studies have refuted it (22,25). Of course, even if ANP suppression does play a role in causing PPV-induced sodium retention and oliguria, it may not explain the reported decrease in GFR caused by PPV.
There are no definitive therapeutic trials for the treatment of PPV- and positive end expiratory pressure (PEEP)-induced renal hypoperfusion and AKI. Several small trials have shown that fluid administration and the use of vasoactive drugs (dopamine at 5 µg/kg per min or fenoldopam) may improve renal function (24,26,27), but results are not consistently positive (for example, no benefit of dopamine at 2 µg/kg per min) (28). It is unlikely that approaches focused solely on the hemodynamic and neurohormonal mechanisms of ALI-induced AKI will be clinically effective in preventing or treating this multifactorial problem, and the development of optimal interventional strategies will require more research into the molecular and cellular mechanisms involved (29).
Inflammatory Mediators and Ventilator-induced Lung and Kidney Injury
ALI is the syndrome of respiratory distress characterized by acute onset, severe hypoxemia, and bilateral radiographic infiltrates in the absence of left atrial hypertension (30). Acute respiratory distress syndrome (ARDS) is the most severe form of ALI, an inflammatory condition characterized by injury to the pulmonary endothelium and epithelium (31). Mounting evidence points to the role of cytokines and chemokines in the pathogenesis of ARDS (30,32,33). Emerging data further suggest that the pro-inflammatory effects of PPV may be a source of AKI, especially in the setting of mechanical ventilation and lung-injurious ventilator strategies (higher tidal volumes and lower PEEP) (34–37). Douillet et al. showed that mechanical ventilation itself can alter the nucleotide and purinoceptor expression in the kidney (38). They used a 4-way rodent model (altering tidal volume and PEEP, as well as the use of a placebo) to show that expression of these stress-responsive molecules is altered even in the presence of lung protective mechanical ventilation strategies (38). Since these extracellular ligands, which help control vascular tone and epithelial/endothelial permeability, are altered by ventilatory strategy, others have looked at the cellular and molecular effects of similar measures. Imai et al. used a rabbit model of ALI (acid aspiration) with both injurious and noninjurious ventilator strategies and variable oxygen and carbon dioxide levels to demonstrate that injurious ventilator strategies precipitate AKI (34). They demonstrated that injurious mechanical ventilation strategies induced production of a variety of inflammatory cytokines (IL-8 and monocyte-chemotactic protein-1, among others). They further demonstrated that this injurious strategy induced epithelial cell apoptosis in both the kidneys and intestines, providing concrete evidence of distant organ cross-talk initiated by ALI. They then showed that plasma from the injurious strategy rabbits induced apoptosis when it was incubated with fresh, healthy rabbit proximal tubular cells (34). Similarly, limited human studies suggest that ALI and PPV play a major role in AKI development. In the ARDS Network tidal volume trial, the low tidal volume group had improved survival and ventilator-free days, along with more days without circulatory, coagulation and renal failure (renal: 20 ± 11 versus 18 ± 11 d, P = 0.005) (37). Furthermore, Ranieri et al. showed in a randomized controlled trial of 44 patients with ARDS that a lung protective mechanical ventilation strategy (lower tidal volumes and higher PEEP) induced a lesser systemic and intrapulmonary inflammatory response (as measured by serum and bronchoalveolar lavage fluid levels of TNF-
, IL-6, and IL-8) than standard of care ventilation (35). Additionally, they were able to show that this same lung protective strategy led to fewer patients with organ system failure, with a greater decrease in the incidence of renal failure (P < 0.04) than any other organ dysfunction (36). The precise pathways and mediators responsible for ventilator-induced injury to the kidneys and other organs have not been elucidated. In addition to a variety of inflammatory cytokines, the nitric oxide pathway has been implicated in this phenomenon.
Nitric oxide, a vasodilator whose metabolites have been shown to exert systemic and renal cytotoxic effects via oxidative stress mediators, has been shown to play key roles in a variety of cellular functions, including vascular and epithelial permeability and apoptosis (39). It is also well documented that nonselective inhibition of nitric oxide synthase (NOS) leads to elevated systemic blood pressure and marked renal vasoconstriction. Using a rodent model of ventilator-induced lung injury, Choi et al. showed that PPV with injurious high tidal volumes (20 ml/kg) induced NOS expression in both the lung and the kidney. At the same time, an increase in systemic microvascular leak was also seen in both organs. This robust detrimental NOS response was blunted when the animals undergoing PPV were adequately fluid resuscitated, and the improvement in renal function was amplified using the NOS inhibitor L-NAME (N-nitro-L-arginine methyl ester). In addition to changes in NOS and its metabolites, they showed that serum vascular endothelial growth factor levels were increased in those animals receiving the lung-injurious ventilation; it is known that nitric oxide increases vascular permeability via extracellular signal-regulated kinases 1 and 2 and vascular endothelial growth factor (40). Thus, it appears that increased vascular permeability and associated cytokine release are contributors to the development of AKI in the setting of PPV. In summary, the decreased morbidity and mortality of patients with ALI achieved with lung-protective strategies for mechanical ventilation are mediated not only by amelioration of ventilator-induced lung injury and inflammation, but also by diminished crosstalk and injury to distant organs, including the kidneys.
Effects of Permissive Hypercapnia
Permissive hypercapnia is a commonly accepted mechanical ventilation practice, in which tidal volumes and alveolar ventilation are reduced to decrease ventilator-induced lung injury while treating ALI. Although it has been assumed that the beneficial effects of this lung-protective ventilatory strategy are the result of decreased stretch, lower pressure, and less mechanical trauma to injured lung, emerging data suggest an independent lung-protective effect of permissive hypercapnia. Although there are no universally accepted guidelines to guide the approach to mechanical ventilation in patients with ALI/ARDS, many physicians use the approach that was successful in the original ARDS Network trial of lower tidal volume ventilation (37). This approach requires use of a tidal volume of 6 ml/kg of ideal body weight and aims to keep static/plateau airway pressure 
30 cmH2O, requiring permissive hypercapnia as needed to avoid ventilator-induced lung injury. Yet despite the use of this approach in clinical practice and in subsequent ARDS Network trials, the approach to permissive hypercapnia and associated acidosis remains an area of clinical uncertainty and practice variation. Intensivists, consulting nephrologists, and other practitioners commonly grapple with questions such as: "How much acidosis is too much acidosis?" and "When should I consider buffering with bicarbonate or renal replacement therapy?" The original ARDS Network low tidal volume trial protocol included arterial pH goals and suggested approaches to the management of acidemia and alkalemia as follows, with an arterial pH goal: 7.30 pH 7.45:
pH < 7.30); 
7.15 (under these conditions, target plateau pressure may be exceeded). Unfortunately, details of the frequency and extent to which these guidelines were applied in this landmark trial have not been published. While the available data do not permit an analysis of any impact of the use and dose of buffer therapy on outcomes, we can infer from the original report that severe acidemia was not commonly encountered. The day 1 pH values for those receiving low tidal volumes were (mean ± SD) 7.38 ± 0.08 (with PaCO2 40 ± 10 mmHg), whereas those for the normal tidal volume group were 7.41 ± 0.07 (with PaCO2 35 ± 8 mmHg). With the pH rising over the course of the next 7 d, there was not an apparent need to use bicarbonate therapy during the course of this trial. Nonetheless, the approach to pH management used in this trial seems sensible and was associated with improved outcomes. We suggest that this approach should be used in clinical practice pending further research in this area. Of course, this approach is intended for patients with ALI, not those with exacerbations of chronically hypercapnic pulmonary diseases such as chronic obstructive pulmonary disease. Many such patients have chronic respiratory acidosis with compensatory metabolic alkalosis; bicarbonate should be used to maintain their plasma bicarbonate concentration at their chronic, pre-exacerbation level (if known), to facilitate liberation from mechanical ventilation when superimposed acute respiratory failure has resolved.
Permissive hypercapnia has a variety of effects, some harmful, others beneficial. In both animal models and human studies, modest hypercapnia has been shown to have reproducible hemodynamic effects that are well tolerated and reversible (41–44). In both canine and human studies, these effects have included a decrease in systemic vascular resistance, and increased cardiac output despite a decrease in cardiac contractility (42–44), although these findings are not consistent in all studies (45). One human study evaluated the effects of buffer therapy for hypercapnic acidosis. Weber et al. investigated the use of tromethamine, a buffer that does not generate CO2 (unlike bicarbonate) for this purpose (44). In this human study, they found that tromethamine raised cardiac contractility and mean arterial pressure (44). Hypercapnia also raises pulmonary vascular resistance, which is potentially harmful in patients with right ventricular dysfunction, including those with pulmonary hypertension caused by ARDS (46,47). Hypercapnic pulmonary vasodilation may also have unfavorable effects on ventilation-perfusion matching and result in increased intrapulmonary shunt with worsening oxygenation in ARDS (46). On the other hand, hypercapnic acidosis also causes a rightward shift of the oxygen-hemoglobin dissociation curve and improves tissue oxygen delivery in shock. Thus, although hypercapnic acidosis may cause or aggravate myocardial depression in critically ill patients, it is generally well tolerated, and buffer therapy should probably be reserved for patients with severe acidemia (pH <7.15). Caution should be exercised in the use of permissive hypercapnia in patients with pulmonary hypertension and right heart failure, in whom associated pulmonary vasoconstriction may have significant adverse hemodynamic effects. Finally, it must be remembered that the use of permissive hypercapnia is contraindicated in patients with raised intracranial pressure (e.g., cerebral edema) because of associated cerebral vasodilation and increased pressure.
What are the beneficial effects of hypercapnic acidosis? Recent analysis of the ARDS Network tidal volume study database suggested an intrinsic benefit from hypercapnia itself, independent of the reduction of minute ventilation and airway pressures (48). Kregenow et al. (48) showed that the adjusted odds ratio for 28-d mortality rate associated with hypercapnic acidosis (defined as pH < 7.35 and a PaCO2 > 45 mmHg) was 0.14 (95% confidence interval, 0.03–0.070; P = 0.016) for those receiving high tidal volumes (12 ml/kg; the injurious ventilation strategy), after controlling for severity of lung injury and comorbidities. Those who received the lung protective strategy (6 ml/kg) had an adjusted ratio of 1.18 (P = not significant), suggesting that hypercapnic acidosis was not of additional benefit in those ventilated with lower, lung-protective tidal volumes. The observed decrease in mortality for those with respiratory acidosis in the high tidal volume arm of the trial is consistent with other emerging data suggesting an independent protective effect of hypercapnic acidosis in the setting of ALI (49–51), and in experimental ischemic-reperfusion injury and shock (46,52,53). Several studies have shown that hypercapnic acidosis attenuates experimental ALI and ventilator-induced lung injury (49,50). Similarly, in isolated perfused animal hearts, hypercapnic acidosis has been shown to have a dose-dependent protective effect against myocardial ischemia-reperfusion injury (53). Similar degrees of metabolic acidosis do not offer the same level of protection from ischemia-reperfusion injury as respiratory acidosis (53). The protective effect of hypercapnic acidosis may result from the inactivation of calcium channels (leading to regional vasodilation), a reduction in cellular oxygen demand (49), or anti-inflammatory effects (50–52). Hypercapnia can decrease the conversion rate of inhibitor of nuclear factor kappa B (I-
B) to nuclear factor kappa B (NF-B), and accordingly decrease the release of cytokines (IL-8 and ICAM-1) that are implicated in the pathogenesis of ALI and AKI (51). Similarly, hypercapnia and associated intracellular acidosis decrease the release of other cytokines (TNF- and IL-1) by inhibition of toll-like receptors (50,52). In summary, through a variety of mechanisms, permissive hypercapnia may favorably influence the course of ALI, associated ventilator-induce lung injury, and organ cross-talk between the injured lung and other organs, leading to a protective effect against the development of AKI. Of course, these experimental data raise obvious concerns regarding potentially deleterious effects of the common practice of using sodium bicarbonate infusions or bicarbonate-buffered renal replacement therapy to provide compensation for respiratory acidosis in mechanically ventilated patients with ALI. However, there is no clinical confirmation of the putative protective effects of hypercapnic acidosis in ALI patients ventilated with low tidal volumes, so the current approach to acid-base management of these complex patients continues to include buffer therapy when severe acidosis develops. We suggest that the guideline for pH management used in the ARDS Network low tidal volume trial is an appropriate approach.
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Pathophysiologic Effects of AKI on Pulmonary Function |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Pulmonary Effects of AKI
Many of the effects of AKI are difficult to identify and quantify independently, but experimental data are increasingly elucidating the subclinical effects of AKI on distant organ function (56). It is obvious that problems such as refractory hyperkalemia, pulmonary edema, or uremic manifestations such as pericarditis are related to AKI when they develop acutely in the appropriate setting. Other uremic manifestations may have several explanations (encephalopathy, acidosis) or may be occult causes of other complications (bleeding diathesis and gastrointestinal bleed, leukocyte dysfunction with immunosuppression and nosocomial infection). In addition to the emerging data that appear to confirm an independent role of AKI in increasing mortality in the ICU, it is also clinically obvious that AKI is a cause of significant morbidity and severely complicates ICU management (57).
It is becoming increasingly clear that the inflammatory response and cytokine cascade that occur in the setting of AKI play a significant role in the development of ALI. Rabb et al. (58) have investigated the mechanisms of the link of AKI and ALI. They demonstrated, in a 4-way rodent model (unilateral ischemic injury, bilateral ischemic injury, bilateral nephrectomy and sham/placebo), that ischemic AKI leads to alteration in pulmonary gene/protein expression (58). Specifically, bilateral ischemic AKI down-regulates the pulmonary expression of all of the following: epithelial sodium channel (eNaC), Na/K ATPase, and aquaporin-5. It should be noted that unilateral ischemic injury did not lead to alteration of the pulmonary expression of these proteins, in contrast to bilateral renal ischemia or nephrectomy. Thus, the observed increase of lung permeability is likely mediated by a systemic effect of AKI, rather than the dose-dependent effect of the "reperfusion products" of ischemic renal injury (58). Subsequently, a variety of animal models have shown that pulmonary expression of these proteins (eNaC, Na/K ATPase, and aquaporins) play important roles in the salt and water/fluid handling and permeability of alveolar epithelium, and dysregulation of these mechanisms may result in the development of ARDS in humans (59–61).
In mice, Hoke et al. used a similar experimental protocol (sham, unilateral renal ischemia, bilateral renal ischemia, and bilateral nephrectomy) and demonstrated that AKI leads to altered pulmonary cytokine expression (62). Similar to the above studies, they showed that bilateral ischemic injury and bilateral nephrectomy were associated with statistically significant increases (compared with unilateral injury and sham) in several serum cytokine levels (IL-1β, IL-6, and IL-12). Of note, there were several other cytokines that increased in the setting of bilateral injury or bilateral nephrectomy, but not both, compared with the same controls (granulocyte macrophage colony-stimulating factor, IL-10, and keratinocyte-derived chemokines) (62). Thus, both models for the acute absence of renal function displayed similar but uniquely different patterns of cytokine expression. Using a similar but not identical protocol, Hassoun et al. demonstrated that the global gene profiles from murine lungs exposed to AKI caused by ischemia-reperfusion or bilateral nephrectomy differed significantly (63). Finally, using the bilateral nephrectomy model, Hoke et al. prophylactically administered the anti-inflammatory agent IL-10; they found prophylaxis with IL-10 decreased the intensity of the inflammatory cascade induced by nephrectomy (62).
Similarly, a rodent ischemia model was used to show that the administration of -melanocyte stimulating hormone immediately before reperfusion (and following ischemic injury) reduced both kidney and lung injury. In addition, this prevented the activation of kidney and lung transcription factors and decreased the expression of stress response genes (TNF- and lung intracellular adhesion molecule-1) (64). It is thought that -melanocyte stimulating hormone acts by inhibition of the activation of transcription factors and stress response genes. This emerging data warrants further investigation of the use of IL-10 and other anti-inflammatory agents as potential therapeutic options for early AKI.
Emerging data continue to underscore the complexity of kidney–lung interaction in AKI. Kim et al. determined in a rodent model that ALI following ischemia-reperfusion is distinct from ALI caused by experimental sepsis (32). Although both the sepsis and ischemia models lead to increased pulmonary vascular permeability and pulmonary histology consistent with ARDS, they were distinct in that the ischemia-induced AKI was associated with lower levels of pulmonary inflammatory cell infiltration, and each animal model had significantly different expression of a variety of heat-shock proteins. Furthermore, pulmonary expression of a variety of cytokines (including TNF- and pro-inflammatory chemokines) differed between animal models of lung injury, indicating that distinct inflammatory mediator profiles were involved in the different injury mechanisms (32). Finally, the phenomenon of distant organ injury resulting in ALI is not unique to renal ischemia, as gut ischemia has been shown to alter systemic cytokine levels (specifically IL-18) and cause inflammatory ALI (65). Specifically, a rodent model of gut ischemia/reperfusion induces a rapid increase of systemic IL-18, peaking at 1-h postreperfusion, paralleled by similar inflammation in lung tissue. The pulmonary inflammation associated with gut ischemia/reperfusion can be augmented by the exogenous administration of IL-18 (65). This research is all the more intriguing when one considers that urinary IL-18 has been shown to be an early diagnostic marker for AKI (and mortality) in patients with ARDS (66) and after cardiac surgery (67).
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Effects of Fluid Management and Renal Replacement Therapy on Pulmonary Function and ALI |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Meanwhile, the correct approach to the use of RRT to control azotemia is increasingly guided by randomized, controlled dosing trials (76–78). However, the correct approach to use of RRT to control fluid balance or buffer permissive hypercapnic respiratory respiratory acidosis is not guided by high-level evidence. As discussed above, emerging experimental evidence suggests that respiratory acidosis may have protective effects in ALI, and buffering with bicarbonate may be harmful, but such correction is commonly made with continuous RRT in patients with combined ALI and AKI (48,50,52). Of course, support with renal replacement therapy has many potentially beneficial effects with patients with combined AKI and ALI. By extrapolation from the literature describing beneficial effects of negative fluid balance in ALI, the use of intermittent or continuous RRT to control fluid balance should have benefit in this patient population. However, there is a lack of clinical trial data to support this assumption. Most trials of RRT to treat patients with ALI have focused on approaches to treat inflammation rather than achieve negative fluid balance.
Continuous hemofiltration with a negative or zero net fluid balance has a hypothesized therapeutic benefit in patients with ALI because of its ability to remove inflammatory and humoral mediators of AKI (and ALI) from the circulation. In addition, patients could derive some therapeutic benefit (improved oxygenation/gas exchange) from fluid removal resulting in decrease pulmonary vascular congestion (lower cardiac filling pressures) if the prescribed therapy maintains even fluid balance (i.e., prevents positive fluid balance) or achieves negative fluid balance. Several animal models (porcine and canine) have reported success in reducing pulmonary edema via these aforementioned mechanisms (79–82). The models used in these studies have varied but include oleic acid-induced ALI (80), endotoxin-induced ALI (79,81), and experimental models of pancreatitis (82). Some of these studies have documented success both clinically as well as via reduced plasma levels of a variety of inflammatory markers, including IL-6 and NF-B (80,82). Similarly, Bellomo et al. showed, in a placebo controlled study of canine endotoxemia/septic shock (independent of ALI) that intensive continuous veno-venous hemofiltration (CVVH), was able to reduce the serum concentration of endothelin-1 and blunt the hypotension (as measured by mean arterial pressure) associated with sepsis (83).
Unfortunately human trials, using modern continuous RRT, have yielded conflicting results. Several studies performed in the late 1980s and 1990s had conflicting results regarding gas exchange and outcomes of patients with ALI receiving RRT (84), but some more recent trials have been encouraging. Honore et al. conducted a prospective interventional trial to examine the effects of short-term, high-volume hemofiltration on 20 patients with septic shock (85). It should be noted that this trial consisted of an initial 4-h period during which 35 L of ultrafiltrate was removed and replaced and a net zero fluid balance was achieved; the patients then went on to receive 96 h of CVVH. This study found that patients who met a preset list of clinical and timed parameters (e.g., mixed venous oxygen saturation, cardiac index) after the initial 4-h period were more likely to have improved outcomes. Caution should be used when interpreting these data as the study was uncontrolled, it was conducted in patients with refractory late septic shock, and only 55% of the study subjects had ALI. Other recent studies investigating the role of RRT specifically in ARDS have had mixed results, in part because of study design limitations. Ronco et al. retrospectively reviewed 80 cases of septic shock associated with ARDS (86). They compared 40 individuals who received early isovolemic hemofiltration with 40 individuals who received conventional therapy. They found that hemofiltration improved oxygenation (as measured by partial pressure of oxygen in arterial blood (Pao2)/(fraction of inspired oxygen (FIO2)) (P < 0.05) and hemodynamic status (as measured by mean arterial pressure and pressor dose) (P < 0.05). In addition, the subjects receiving the early hemofiltration had shorter ICU stays (P < 0.002) and improved 28-d survival (55% versus 27.5%, P < 0.05) (86). Some of these findings were supported by a smaller uncontrolled, prospective study of 10 children with ARDS associated with cancer therapy. In this trial, only 4 of the 10 children had AKI, but all underwent early continuous venovenous hemodiafiltration to achieve a negative or zero fluid balance. Ninety percent of the subjects achieved resolution of their ARDS, with 8 of the 10 patients alive at the 18-mo follow-up (87). On the other hand, Hoste et al. (84) conducted a retrospective study of 37 patients with AKI and ALI, all of whom underwent continuous venovenous hemodiafiltration. They found no benefit when comparing hemodynamics (e.g., mean arterial pressure, central venous pressure), mechanical ventilation requirements (e.g., FIO2, PEEP), or gas exchange (e.g., partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood) parameters from 24 h before RRT initiation with those from the first 24 h after initiation. Unfortunately, this retrospective study did not deliver optimal RRT with blood flow rates being set at 100 ml/min and dialysate flow at 1.0 L/h. It is clear that additional prospective trials are required to determine the optimal approach to delivery of RRT in the treatment of patients with AKI and ALI (84).
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Conclusion |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Disclosures |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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Footnotes |
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References |
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TopIntroductionRenal Effects of ALI...Effects of Mechanical...Pathophysiologic Effects of AKI...Effects of Fluid Management...ConclusionDisclosuresReferences |
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