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CHAPTER 97: Acute Kidney Injury 929

solutes. However, the precise mechanism is not well understood. In Prevention of nephrotoxic injury is the other mainstay of AKI preven-
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a porcine kidney model, infusion of either 10% HES 200/0.5, 6% HES tion in critically ill patients. Avoidance of potential nephrotoxins such as
130/0.42 or Ringer lactate (RL) was performed to achieve a hematocrit intravenous radiocontrast, aminoglycosides, amphotericin, and NSAIDs
of 20% which was then maintained. Pathophysiological measurements is prudent, when possible. Single daily dosing of aminoglycoside anti-
(including creatinine clearance and colloid oncotic pressure measure- biotics is associated with a lower risk of nephrotoxicity and equivalent
ments) and histological examination was carried out. The lesions of antimicrobial efficacy compared to multiple dosing strategies. 39-41 Drug
osmotic nephrosis were present in all groups but were more severe in modifications such as nonionic radiocontrast 46,47 and lipid-emulsified
the two HES groups. Lesions appeared as early as 6 hours after exposure. amphotericin B may also reduce the incidence of ATN. Aggressive diuresis
The 10% HES 200/0.5 group was associated with more severe interstitial must be avoided when possible, particularly in conjunction with the use of
inflammation. 126 ACEIs or ARBs, and must be accompanied by careful monitoring of fluid
The recently published Crystalloid versus Hydroxyethyl Starch Trial balance and renal function. Monitoring the serum levels of potentially
(CHEST) attempted to evaluate the safety and efficacy of an isotonic nephrotoxic drugs such as aminoglycosides, cyclosporine, tacrolimus, and
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HES preparation. Almost 7000 ICU patients were enrolled and random- vancomycin is recommended, although studies proving that therapeutic
ized to receive 6% HES (130/0.4) in 0.9% saline solution or 0.9% saline drug monitoring decreases the incidence of ATN are lacking.
solution for volume resuscitation. There was no significant difference in Numerous studies have sought to demonstrate efficacy of pharma-
90-day mortality between the two groups (18% in the HES group and cologic interventions for primary prevention of AKI (prophylaxis), or
17% in the saline group; RR in the HES group, 1.06; 95% CI, 0.96-1.18; secondary prevention in AKI (ATN therapy to decrease dialytic require-
p = 0.26). In the HES and saline groups, renal injury occurred in 34.6% ment and improve outcome). Broadly speaking, these studies have been
and 38.0% of patients, respectively (p = 0.005), and renal failure occurred trials of diuretics or renal vasodilators.
in 10.4% and 9.2% of patients, respectively (p = 0.12). More patients who
group (RR 1.21; 95% CI, 1.00 to 1.45; p = 0.04). HES was associated with ■ DIURETICS
received HES required RRT, 7% in the HES group and 5.8% in the saline
significantly more adverse events (5.3% vs 2.8%, p < 0.001). 127 Furosemide is a loop diuretic and vasodilator that may decrease oxygen
A recently published Cochrane review concluded that there was no consumption in the loop of Henle by inhibiting sodium transport, thus
evidence that colloids reduced the risk of death compared to crystal- potentially lessening ischemic injury. By increasing urinary flow, it may
loids when used for resuscitation on patients following burns, trauma, also reduce intratubular obstruction and back leakage of filtrate. A
or surgery. Given the toxicity concerns with HES preparations and the number of studies have examined the role of furosemide in the preven-
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lack of evidence of superiority of colloids over crystalloids, there is no tion and treatment of AKI. A meta-analysis including nine randomised
rationale to support their routine use in preference to crystalloid therapy. controlled trials totalling 849 patients with or at risk of acute renal
However, colloids may still be of benefit in certain patient populations, failure concluded that furosemide treatment did not significantly alter
and the relative risks and benefits of different colloids and crystalloids in-hospital mortality (RR 1.11, 95% CI 0.92-1.33), risk for requiring
remains an active area of research and debate. Concerning vasopres- RRT (RR 0.99, 95% CI 0.80-1.22), dialysis sessions required, and pro-
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sors and inotropes, there are no proven advantages of any specific agent portion of patients with persistent oliguria. Stratifying studies that
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with respect to renal function. A large RCT involving 1679 patients used furosemide to prevent or treat acute renal failure did not change
compared norepinephrine and dopamine as first line vasopressors in the results on mortality and the risk for requiring dialysis (RR 4.12, 95%
the treatment of shock. There was no difference in mortality or renal CI 0.46-37.2). High-dose furosemide (1-3.4 g/d) was associated with an
function between the two groups, but dopamine therapy was associated increased risk of temporary deafness and tinnitus. An update of this
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with more arrhythmias. A subgroup analysis showed that dopamine was meta-analysis which included 11 studies and 962 patients confirmed the
associated with an increased risk of death at 28 days in patients with car- earlier findings; furosemide did not appear to reduce the risk of requir-
diogenic shock. Vasopressin is occasionally used in shock refractory to ing RRT (RR 1.02, 95% CI 0.90-1.16, p = 0.73) and hospital mortality
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norepinephrine. It is a peptide hormone which induces vasoconstriction (RR 1.12, 95% CI 0.93-1.34, p = 0.23) when used as a preventive or
through activation of V1 receptors on vascular smooth muscle. It did not therapeutic drug in patients at risk of or with established AKI. The
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reduce mortality or need for RRT compared to norepinephrine in a RCT primary prevention studies included general, vascular, and cardiac
involving 778 patients. 131 surgery patients, as well as patients undergoing coronary angiography.
Among interventions which have been found potentially beneficial in It was shown that the mortality rate of oliguric patients who
septic patients in recent years, including the use of early goal-directed responded to furosemide with a diuresis was lower than those who did
therapy, corticosteroids, and activated protein C, none have been shown not. 138,139 However, the clinical characteristics, severity of renal failure,
to decrease the incidence or severity of AKI. Limited evidence suggests and mortality rates were similar in patients with either spontaneous
that lung-protective mechanical ventilation strategies may decrease the nonoliguric ARF or patients who became nonoliguric after furosemide.
adverse renal impact of positive pressure ventilation. Early evidence sug- This implies that those patients able to respond to furosemide have less
gested that intensive insulin therapy may be associated with a reduced severe renal damage than nonresponders, rather than deriving any true
incidence of AKI. A systematic review of three RCTs investigating therapeutic benefit from furosemide administration.
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the association between tight glycemic control and AKI involving A retrospective review of a recent trial in critically ill patients with
2684 patients demonstrated a 38% risk reduction of AKI in the intensive ATN raised concerns of possible harm from loop diuretics in AKI. The
control group. However, intensive therapy was associated with a fourfold authors found that diuretic use was associated with an increased risk of
increased risk of hypoglycemia. In a meta-analysis of 29 RCTs total- death and nonrecovery of renal function. Most of the increased risk,
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ing 8432 patients, no difference in mortality was observed in 27 of the however, was seen in those patients unresponsive to high doses of diuret-
studies. New need for dialysis was reported in 9 trials, 8 of which were ics, implying they had more severe disease. Therefore, diuretics should
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published. There was no significant association between tight glucose be used with caution in critically ill patients, and iatrogenic hypovolemia
control and a new need for RRT overall (11.2% vs 12.1%; RR, 0.96; 95% and superimposed prerenal azotemia must be avoided. Diuretics should
CI, 0.76-1.20). The NICE-SUGAR trial randomised 6104 ICU patients be withdrawn if there is no response, to avoid ototoxicity. Our current
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to intensive or conventional glucose control. The authors reported no maximal, synergistic diuretic challenge combines furosemide 200 mg IV
difference in need for RRT between groups but an increase in mortal- with chlorothiazide 500 mg IV. In patients who experience an increase
ity and hypoglycemia in the intensive control group. Tight glycemic in urine output, hypotension must be avoided, since kidneys with ATN
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control in critically ill patients is not therefore generally recommended; are susceptible to further damage from decreases in perfusion pressure.
certainly not to prevent or ameliorate AKI. 7 To maintain the diuresis, a continuous infusion of drug is theoretically

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