Dangers of hyperoxia Singer, Mervyn; Young, Paul J; Laffey, John G ...
Critical care,
12/2021, Letnik:
25, Številka:
1
Journal Article
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Oxygen (O
) toxicity remains a concern, particularly to the lung. This is mainly related to excessive production of reactive oxygen species (ROS). Supplemental O
, i.e. inspiratory O
concentrations ...(F
O
) > 0.21 may cause hyperoxaemia (i.e. arterial (a) PO
> 100 mmHg) and, subsequently, hyperoxia (increased tissue O
concentration), thereby enhancing ROS formation. Here, we review the pathophysiology of O
toxicity and the potential harms of supplemental O
in various ICU conditions. The current evidence base suggests that PaO
> 300 mmHg (40 kPa) should be avoided, but it remains uncertain whether there is an "optimal level" which may vary for given clinical conditions. Since even moderately supra-physiological PaO
may be associated with deleterious side effects, it seems advisable at present to titrate O
to maintain PaO
within the normal range, avoiding both hypoxaemia and excess hyperoxaemia.
During hemorrhagic shock, blood loss causes a fall in blood pressure, decreases cardiac output, and, consequently, O
transport. The current guidelines recommend the administration of vasopressors in ...addition to fluids to maintain arterial pressure when life-threatening hypotension occurs in order to prevent the risk of organ failure, especially acute kidney injury. However, different vasopressors exert variable effects on the kidney, depending on the nature and dose of the substance chosen as follows: Norepinephrine increases mean arterial pressure both via its α-1-mediated vasoconstriction leading to increased systemic vascular resistance and its β1-related increase in cardiac output. Vasopressin, through activation of V1-a receptors, induces vasoconstriction, thus increasing mean arterial pressure. In addition, these vasopressors have the following different effects on renal hemodynamics: Norepinephrine constricts both the afferent and efferent arterioles, whereas vasopressin exerts its vasoconstrictor properties mainly on the efferent arteriole. Therefore, this narrative review discusses the current knowledge of the renal hemodynamic effects of norepinephrine and vasopressin during hemorrhagic shock.
Activation of arginine–vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces vasoconstriction through the ...activation of V1a receptors located on vascular smooth muscle cells. Due to its non-selective receptor affinity arginine–vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand’s factor and platelet activation. Finally, it also cross-activates oxytocin receptors. During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation. Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects. In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery. Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events. Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.
Guidelines recommend that a mean arterial pressure (MAP) value greater than 65 mm Hg should be the initial blood pressure target in septic shock, but what evidence is there to support this statement? ...We searched Pubmed and Google Scholar by using the key words 'arterial pressure', 'septic shock', and 'norepinephrine' and retrieved human studies published between 1 January 2000 and 31 July 2014. We identified seven comparative studies: two randomized clinical trials and five observational studies. The results of the literature review suggest that a MAP target of 65 mm Hg is usually sufficient in patients with septic shock. However, a MAP of around 75 to 85 mm Hg may reduce the development of acute kidney injury in patients with chronic arterial hypertension. Because of the high prevalence of chronic arterial hypertension in patients who develop septic shock, this finding is of considerable importance. Future studies should assess interactions between time, fluid volumes administered, and doses of vasopressors.
Background
A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that ...SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (
C
RS
), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS.
Methods
Gas exchanges,
C
RS
and hemodynamics were assessed at 2 levels of PEEP (15 cmH
2
O and 5 cmH
2
O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH
2
O and the volume predicted by compliance at PEEP 5 cmH
2
O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and
C
RS
at PEEP 5 cmH
2
O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients.
Results
The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median interquartile range 0.7 0.55–0.94) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 0.31–0.48). The PaO
2
/FiO
2
ratio at PEEP 15 cmH
2
O was higher compared to PEEP 5 cmH
2
O only in highly recruitable patients (173 139–236 vs 135 89–167 mmHg;
p
< 0.01). Neither PaO
2
/FiO
2
or
C
RS
measured at PEEP 15 cmH
2
O or at PEEP 5 cmH
2
O nor changes in PaO
2
/FiO
2
or
C
RS
in response to PEEP changes allowed to identify highly or poorly recruitable patients.
Conclusion
In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.
Purpose
Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic ...hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.
Methods
We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.
Results
Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction
p
= 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).
Conclusions
Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.
Abstract
Rationale
Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid ...therapy.
Objectives
To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP).
Methods
We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics.
Measurements and main results
Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio aHR 1.29; 95% confidence interval 95% CI 1.05–1.58;
P
= 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53;
P
= 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60;
P
= 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61;
P
= 0.0003).
Conclusions
Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.
There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO
) and fluid resuscitation with hypertonic saline solution in patients with ...septic shock. We tested whether these interventions are associated with reduced mortality.
This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO
at 1·0 (hyperoxia) or FiO
set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422.
Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia n=223 or hyperoxia n=219; isotonic n=224 or hypertonic n=218). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio HR 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 85%) and normoxia groups (165 76%; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 11% vs 13 6%; p=0·06) and atelectasis (26 12% vs 13 6%; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23).
In patients with septic shock, setting FiO
to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival.
The French Ministry of Health.
Purpose
Septic shock-induced disseminated intravascular coagulopathy (DIC) contributes to multiple organ failure. Mechanisms governing vascular responses to open occurrence of DIC have not yet been ...established. Circulating plasma microparticles (MPs), released upon cell stress, constitute a catalytic procoagulant surface and are surrogates of vascular cell activation/injury. Herein, MPs were assessed as possible markers of haemostatic and vascular dysfunction in the DIC time course.
Methods
One hundred patients with septic shock from three ICUs were enrolled and their haemostatic status evaluated at admission (D1), D2, D3 and D7. Circulating procoagulant MPs were isolated, quantified by prothrombinase assay and their cellular origin determined. DIC diagnosis was made according to the JAAM 2006 score.
Results
Ninety-two patients were analysed and 40 had DIC during the first 24 h. Routine clotting times and factor/inhibitor activity did not allow assessing vascular cell involvement. At admission, thrombin generation and fibrinolysis were observed in both groups while impaired fibrin polymerisation was evidenced only in DIC patients. Sustained thrombin generation persisted over time in both groups at D7. While total microparticle concentrations were in the same range regardless of DIC diagnosis, specific phenotypes were already detected at admission in DIC patients. Endothelial- and leucocyte-derived MPs were higher in DIC while an increased soluble glycoprotein V/platelet ratio was delayed, underscoring the first involvement of endothelial cells and leucocytes whereas platelet activation was delayed. Endothelium-derived CD105-MPs (OR 6.55) and CD31-MPs (OR 0.49) were strongly associated with early DIC in multivariate analysis.
Conclusion
Endothelial-derived microparticles are relevant biomarkers of septic shock-induced DIC and could be used to evaluate early vascular injury.
Abstract
Background
Except in a few retrospective studies mainly including patients under chemotherapy, information regarding the impact of immunosuppressive therapy on the prognosis of patients ...admitted to the intensive care unit (ICU) for septic shock is scarce. Accordingly, the PACIFIC study aimed to asses if immunosuppressive therapy is associated with an increased mortality in patients admitted to the ICU for septic shock.
Methods
This was a retrospective epidemiological multicentre study. Eight high enroller centres in septic shock randomised controlled trials (RCTs) participated in the study. Patients in the “exposed” group were selected from the screen failure logs of seven recent RCTs and excluded because of immunosuppressive treatment. The “non-exposed” patients were those included in the placebo arm of the same RCTs. A multivariate logistic regression model was used to estimate the risk of death.
Results
Among the 433 patients enrolled, 103 were included in the “exposed” group and 330 in the “non-exposed” group. Reason for immunosuppressive therapy included organ transplantation (n = 45 44%) or systemic disease (n = 58 56%). ICU mortality rate was 24% in the “exposed” group and 25% in the “non-exposed” group (
p
= 0.9). Neither in univariate nor in multivariate analysis immunosuppressive therapy was associated with a higher ICU mortality (OR: 0.95; 95% CI 0.56–1.58:
p
= 0.86 and 1.13 95% CI 0.61–2.05:
p
= 0.69, respectively) or 3-month mortality (OR: 1.13; 95% CI 0.69–1.82:
p
= 0.62 and OR: 1.36 95% CI 0.78–2.37:
p
= 0.28, respectively).
Conclusions
In this study, long-term immunosuppressive therapy excluding chemotherapy was not associated with significantly higher or lower ICU and 3-month mortality in patients admitted to the ICU for septic shock.