Abstract
As we were taught, for decades, that iodinated contrast-induced acute kidney injury should be dreaded, considerable efforts were made to find out effective measures in mitigating the renal ...risk of iodinated contrast media. Imaging procedures were frequently either downgraded (unenhanced imaging) or deferred as clinicians felt that the renal risk pertaining to contrast administration outweighed the benefits of an enhanced imaging. However, could we have missed the point? Among the abundant literature about iodinated contrast-associated acute kidney injury, recent meaningful advances may help sort out facts from false beliefs. Hence, there is increasing evidence that the nephrotoxicity directly attributable to modern iodinated CM has been exaggerated. Failure to demonstrate a clear benefit from most of the tested prophylactic measures might be an indirect consequence. However, the toxic potential of iodinated contrast media is well established experimentally and should not be overlooked completely when making clinical decisions. We herein review these advances in disease and pathophysiologic understanding and the associated clinical crossroads through a typical case vignette in the critical care setting.
1 regarding the hemodynamic management in the prevention and treatment of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) 1. Besides discussing the management of ...intravascular volume and blood pressure, the authors provide an insightful perspective on increasing cardiac output (CO) to enhance oxygen delivery to brain regions affected by vasospasm, a significant contributor to DCI. ...milrinone exhibits vasodilatory properties through the inhibition of the phosphodiesterase within vascular smooth muscle, mediated by protein kinase and myosin light chain kinase intracellular pathways 2. ...through its relaxant effect, IV milrinone may serve as an alternative to endovascular angioplasty (intraarterial infusion vasodilators and/or balloon angioplasty).
As we were taught, for decades, that iodinated contrast-induced acute kidney injury should be dreaded, considerable efforts were made to find out effective measures in mitigating the renal risk of ...iodinated contrast media. Imaging procedures were frequently either downgraded (unenhanced imaging) or deferred as clinicians felt that the renal risk pertaining to contrast administration outweighed the benefits of an enhanced imaging. However, could we have missed the point? Among the abundant literature about iodinated contrast-associated acute kidney injury, recent meaningful advances may help sort out facts from false beliefs. Hence, there is increasing evidence that the nephrotoxicity directly attributable to modern iodinated CM has been exaggerated. Failure to demonstrate a clear benefit from most of the tested prophylactic measures might be an indirect consequence. However, the toxic potential of iodinated contrast media is well established experimentally and should not be overlooked completely when making clinical decisions. We herein review these advances in disease and pathophysiologic understanding and the associated clinical crossroads through a typical case vignette in the critical care setting. Keywords: Contrast media (MeSH: D003287), Intensive care units (MeSH D007362), Drug-related side effects and adverse reactions (MeSH D064420), Tomography scanners, X-ray computed (MeSH: D015898), Percutaneous coronary interventions (MeSH: D062645), Contrast-induced nephropathy, Post-contrast acute kidney injury
Purpose
Critically ill patients, among whom acute kidney injury is common, are often considered particularly vulnerable to iodinated contrast medium nephrotoxicity. However, the attributable ...incidence remains uncertain given the paucity of observational studies including a control group. This study assessed acute kidney injury incidence attributable to iodinated contrast media in critically ill patients based on new data accounting for sample and effect size and including a control group.
Methods
Systematic review of studies measuring incidence of acute kidney injury in critically ill patients following contrast medium exposure compared to matched unexposed patients. Patient-level meta-analysis implementing a Bayesian nested mixed effects multiple logistic regression model.
Results
Ten studies were identified; only four took into account the baseline acute kidney injury risk, three by patient matching (560 patients). Objective meta-analysis of these three studies (vague and impartial a priori hypothesis concerning attributable acute kidney injury risk) did not find that iodinated contrast media increased the incidence of acute kidney injury (odds ratio 0.95, 95% highest posterior density interval 0.45–1.62). Bayesian analysis demonstrated that, to conclude in favor of a statistically significant incidence of acute kidney injury attributable to contrast media despite this observed lack of association, one’s a priori belief would have to be very strongly biased, assigning to previous uncontrolled reports 3–12 times the weight of evidence strength provided by the matched studies including a control group.
Conclusions
Meta-analysis of matched cohort studies of iodinated contrast medium exposure does not support a significant incidence of acute kidney injury attributable to iodinated contrast media in critically ill patients.
Purpose
Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of ...invasive mechanical ventilation.
Methods
ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality.
Results
1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI
95
) 0.71–0.87 and 0.71 CI
95
0.61–0.81 in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 7–21 vs 6 3–11 days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure).
Conclusions
In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.
Background
Intravenous (IV) milrinone, in combination with induced hypertension, has been proposed as a treatment option for cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). ...However, data on its safety and efficacy are scarce.
Methods
This was a controlled observational study conducted in an academic hospital with prospectively and retrospectively collected data. Consecutive patients with cerebral vasospasm following aSAH and treated with both IV milrinone (0.5 µg/kg/min
−1
, as part of a strict protocol) and induced hypertension were compared with a historical control group receiving hypertension alone. Multivariable analyses aimed at minimizing potential biases. We assessed (1) 6-month functional disability (defined as a score between 2 and 6 on the modified Rankin Scale) and vasospasm-related brain infarction, (2) the rate of first-line or rescue endovascular angioplasty for vasospasm, and (3) immediate tolerance to IV milrinone.
Results
Ninety-four patients were included (41 and 53 in the IV milrinone and the control group, respectively). IV milrinone infusion was independently associated with a lower likelihood of 6-month functional disability (adjusted odds ratio aOR = 0.28, 95% confidence interval CI = 0.10–0.77) and vasospasm-related brain infarction (aOR = 0.19, 95% CI 0.04–0.94). Endovascular angioplasty was less frequent in the IV milrinone group (6 15% vs. 28 53% patients,
p
= 0.0001, aOR = 0.12, 95% CI 0.04–0.38). IV milrinone (median duration of infusion, 5 2–8 days) was prematurely discontinued owing to poor tolerance in 12 patients, mostly (
n
= 10) for “non/hardly-attained induced hypertension” (mean arterial blood pressure < 100 mmHg despite 1.5 µg/kg/min
−1
of norepinephrine). However, this event was similarly observed in IV milrinone and control patients (
n
= 10 24% vs.
n
= 11 21%, respectively,
p
= 0.68). IV milrinone was associated with a higher incidence of polyuria (IV milrinone patients had creatinine clearance of 191 153–238 ml/min
−1
) and hyponatremia or hypokalemia, whereas arrhythmia, myocardial ischemia, and thrombocytopenia were infrequent.
Conclusions
Despite its premature discontinuation in 29% of patients as a result of its poor tolerance, IV milrinone was associated with a lower rate of endovascular angioplasty and a positive impact on long-term neurological and radiological outcomes. These preliminary findings encourage the conduction of confirmatory randomized trials.
Purpose
The use of arterial partial pressure of carbon dioxide (PaCO
2
) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We ...aimed to describe targets for PaCO
2
in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO
2
values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO
2
with in-hospital mortality.
Methods
We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO
2
was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO
2
> 35 and to 45 mmHg; mild hypocapnia as 32–35 mmHg; severe hypocapnia as 26–31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg.
Results
1476 patients (65.9% male, mean age 52
±
18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO
2
had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus
p
value = 0.0009). Important differences were observed across different subgroups of ABI patients.
Conclusions
Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO
2
values were significantly associated with increased in-hospital mortality.
There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care ...populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.
In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).
We included 1217 patients (mean age 51.2 years SD 18.1, 66% male, mean body mass index BMI 26.3 SD 5.18) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min IQR 9.2-15.1, 13 J/min IQR 10-17, and 14 J/min IQR 11-20, respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).
Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.
...it was (Table 1, fourth row): causal aneurysm was located in the anterior circulation in 30 (73%) and 46 (89%) patients in the intravenous (IV) milrinone and the control group, respectively (p = ...0.06). Whether the remainder of this surveyed population of physicians perform a daily comprehensive examination of all large cerebral arteries is highly uncertain. Because cerebral arteries other than the MCA were seldom studied by ultrasound in the Milrispasm study 1, we preferred to only mention the MCA in the article. ...a possible delay in the diagnosis of vasospasm (a delay related to the fact that posterior circulation has been overlooked) would have impacted the between-group difference in long-term outcomes only if a change in ultrasound practice would have occurred between the two study periods, i.e., between the two groups of this before-and-after study.
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