Prevalence of hypophosphatemia in the ICU - Results of an international one-day point prevalence survey.

BACKGROUND & AIMS: Hypophosphatemia (HypoP) is associated with organ dysfunction and mortality. Despite its potential severe consequences, HypoP remains poorly characterized in terms of real prevalence and timing of onset. The primary objective was to determine the prevalence of HypoP defined as blood phosphate <0.8 and < 0.65 mmol/l on one particular day at international level. METHODS: One-day point prevalence survey conducted by the Section of Metabolism, Endocrinology and Nutrition (MEN) of the European Society of Intensive Care Medicine (ESICM) during week 11-2020. RESULTS: In total, 56 adult and 4 paediatric ICUs, from 22 countries participated: 41 ICUs were mixed medico surgical, the 19 others being cardiac, medical or surgical. Phosphate measurements were performed daily in 21 ICUs, and 1-3 times per week in 39 ICUs. On D-Day 909 patients (883 adults) were present and 668/883 (75.7%) had serum/plasma phosphate determined, revealing a HypoP in 103 (15.4%) patients aged 62 [18 to 85] years. Of those, 49 patients presented phosphate <0.65 mmol/l: cases of hypophosphatemia were detected at any time of patient's ICU stay. No HypoP was observed in children. A treatment protocol existed only in 41.1% of adult ICUs, independently of ICU type, or size. Only 41/98 of the HypoP patients (29/41 of patients with phosphate <0.65 mmol/l) were receiving phosphate. CONCLUSION: HypoP is present at least in 15.4% of ICU patients, and may occur at any time during the ICU stay. The absence of phosphate repletion protocols in 60% of participating ICUs is an unexpected finding, and confirms the necessity for the development of ICU phosphate protocols and guidelines. CLINICALTRIALS IDENTIFIER: NCT04201899.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

PURPOSE: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS: International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS: The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION: Consensus was reached on a future research agenda for the AKI section of the ESICM.

Effect of flumazenil on diaphragm electrical activation during weaning from mechanical ventilation after acute respiratory distress syndrome.

BACKGROUND: Diaphragm electrical activation (EAdi) and the ratio of tidal volume to EAdi (VT/EAdi) may provide clinical information on neuroventilatory efficiency (NVE) in patients being weaned from mechanical ventilation. We tested the hypothesis that residual sedation could interfere with respiratory recovery, by assessing the effects of flumazenil on EAdi and VT/EAdi ratio. METHODS: This observational study included 13 patients breathing with pressure-support ventilation (PSV) after a long period of controlled mechanical ventilation (i.e. >4 days) plus midazolam-based sedation for acute respiratory distress syndrome. EAdi and respiratory patterns were compared before and after a bolus of flumazenil, which was given because neurological status needed to be evaluated. RESULTS: Flumazenil induced a significant increase in EAdi [+71 (41-123)%, P=0.0002] and VT [+17 (8-32)%, P=0.0005], resulting in significantly decreased NVE [-34 (15-43)%]. The increased VT was significantly correlated with the increased EAdi (ρ=0.70, P=0.009). CONCLUSIONS: During weaning from mechanical ventilation, the diaphragmatic contribution to the breathing process may be reduced by residual midazolam-induced ventilatory depression. The increased EAdi with reversal of residual sedation was associated with a proportional increase in VT. These findings should be considered by the attending physician when interpreting daily EAdi and VT changes during weaning from mechanical ventilation.

Facing acid-base disorders in the third millennium - the Stewart approach revisited.

Acid-base disorders are common in the critically ill. Most of these disorders do not cause harm and are self-limiting after appropriate resuscitation and management. Unfortunately, clinicians tend to think about an acid-base disturbance as a "disease" and spend long hours effectively treating numbers rather than the patient. Moreover, a sizable number of intensive-care physicians experience difficulties in interpreting the significance of or understanding the etiology of certain forms of acid-base disequilibria. Traditional tools for interpreting acid-base disorders may not be adequate for analyzing the complex nature of these metabolic abnormalities. Inappropriate interpretation may also lead to wrong clinical conclusions and incorrectly influence clinical management (eg, bicarbonate therapy for metabolic acidosis in different clinical situations). The Stewart approach, based on physicochemical principles, is a robust physiological concept that can facilitate the interpretation and analysis of simple, mixed, and complex acid-base disorders, thereby allowing better diagnosis of the cause of the disturbance and more timely treatment. However, as the concept does not attach importance to plasma bicarbonate, clinicians may find it complicated to use in their daily clinical practice. This article reviews various approaches to interpreting acid-base disorders and suggests the integration of base-excess and Stewart approach for a better interpretation of these metabolic disorders.

Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study.

BACKGROUND: Respiratory variation in pulse pressure (ΔPP) is commonly used to predict the fluid responsiveness of critically ill patients. However, some researchers have demonstrated that this measurement has several limitations. The present study was designed to evaluate the proportion of patients satisfying criteria for valid application of ΔPP at a given time-point. METHODS: A 1 day, prospective, observational, point-prevalence study was performed in 26 French intensive care units (ICUs). All patients hospitalized in the ICUs on the day of the study were included. The ΔPP validity criteria were recorded prospectively and defined as follows: (i) mechanical ventilation in the absence of spontaneous respiration; (ii) regular cardiac rhythm; (iii) tidal volume ≥8 ml kg(-1) of ideal body weight; (iv) a heart rate/respiratory rate ratio >3.6; (v) total respiratory system compliance ≥30 ml cm H2O(-1); and (vi) tricuspid annular peak systolic velocity ≥0.15 m s(-1). RESULTS: The study included 311 patients with a Simplified Acute Physiology Score II of 41 (39-43). Overall, only six (2%) patients satisfied all validity criteria. Of the 170 patients with an arterial line in place, only five (3%) satisfied the validity criteria. During the 24 h preceding the study time-point, fluid responsiveness was assessed for 79 patients. ΔPP had been used to assess fluid responsiveness in 15 of these cases (19%). CONCLUSIONS: A very low percentage of patients satisfied all criteria for valid use of ΔPP in the evaluation of fluid responsiveness. Physicians must consider limitations to the validity of ΔPP before using this variable.

Phosphate induced crystal acute kidney injury - an under-recognized cause of acute kidney injury potentially leading to chronic kidney disease: case report and review of the literature.

Acute phosphate nephropathy or nephrocalcinosis is a tubulointerstitial nephropathy characterized by tubular calcium phosphate deposition - crystal nephropathy - and slowly progressive renal insufficiency during or following treatment with preparations containing sodium phosphate. We report a patient who developed nephrocalcinosis (crystal induced acute kidney injury) following the administration of a combination of oral and rectal sodium phosphate for treatment of postoperative constipation. A timely renal replacement therapy procedure may reverse the process of crystallization and the irreversible slope towards chronic dialysis.

New insights regarding rationale, therapeutic target and dose of hemofiltration and hybrid therapies in septic acute kidney injury.

Mediator removal from tissue (capillary blood compartment, CABC) and transport to the central circulation (central blood compartment, CEBC) must be effective. Effectiveness through a passive mechanism seems unlikely as the surface of CEBC (30 m(2)) is smaller than CABC (300 m(2)) whereby the former will be a limiting factor in passive transport. According to studies, a high exchange volume can induce an 80-fold increase in lymphatic flow. This results in displacement (active transport) of mediators to CEBC. Recent studies have shown that the delivered dose constitutes the mainstay of continuous renal replacement therapy. However, these results are not likely to change the recommendation: 35 ml/kg/h, adjusted for predilution, in septic acute kidney injury (AKI). Recently, studies were focusing on global intensive care unit AKI. In non-septic AKI, those studies show that 20-25 ml/kg/h was optimal. The DO-RE-MI trial underscored the importance of delivery which could be obtained by targeting doses between 5 and 10 ml/kg/h higher than prescribed. Until the IVOIRE trial becomes available, septic AKI should be treated by continuous veno-venous hemofiltration at 35 ml/kg/h. In non-septic AKI, 25 ml/kg/h remains optimal.

Septic acute kidney injury: the culprit is inflammatory apoptosis rather than ischemic necrosis.

For a long time, acute kidney injury (AKI) was considered to be a primarily hemodynamic condition characterized by a reduction of renal blood flow, induced by either cardiogenic or distributive (septic) shock. Consequently, all efforts to treat AKI were essentially concentrated on increasing renal flow by enhancing cardiac flow output and perfusion pressure. At the beginning of this decade, Bellomo and co-workers produced new and intriguing data in an animal model of septic AKI that undermined existing concepts. They observed that medullar and cortical renal blood flow were both maintained and even increased in septic shock, underscoring that septic AKI was a totally different physiological phenomenon than nonseptic AKI. Also, apoptosis was found to play a more important role in sepsis and septic shock than pure necrosis. Despite these findings, the role of apoptosis as a main mechanism of organ dysfunction remains topic of debate.

Continuous hemofiltration in 2009: what is new for clinicians regarding pathophysiology, preferred technique and recommended dose?

In the last years, publications have questioned the classical dose of 35 ml/kg, but are those studies strong enough in terms of scientific power in order to change our practice? We will try to settle some recommendations for clinicians. Manipulation of dose, porosity, and combinations have yielded promising findings. However, conclusive evidence based on randomized trials remains scarce, limiting the practical implementation in daily practice. From the few designed studies, it is safe to say that optimization of delivered dose has a proven positive effect. An ultrafiltration rate of around 35 ml/kg/h, with adjustment for predilution, can be recommended for the septic patient. Recent studies do not have enough power to change this recommendation in view of its shortcomings. Finally the recommendation is to keep going with a continuous technique, a pure continuous veno-venous hemofiltration mode, and at a dose of 35 ml/kg/h while waiting for other studies to be published.

[High-volume hemofiltrations].

Almost 10 years ago, standard hemofiltration (HF) was carried out at an ultrafiltration (UF) rate of not more than 2 1/hour and only a predilution variant was usually used. However, after Ronco published the results of his study early in the 20th century the situation changed as this study provided evidence that increasing an UF rate up to 35 ml/kg/hr had a positive effect in patients with acute renal failure (ARF). At the same time, there was a new standard for the determination of high-volume HF (HVHF) and new concepts generalized in this paper have emerged. Moreover, two different procedures of HVHF: (1) a continuous high-volume technique providing a rate of 50-70 ml/kg/hr during 24 hours; (2) an intermittent high-volume technique, the so-called HVHF with short courses of treatment, a very high volume at a rate of 100-120 ml/kg/hr during 4-8 hours. Later on this technique came to be called pulse HVHF. Both methods are designated by the abbreviation HVHF, but their concepts and results are slightly different, as will be discussed below. As for the higher doses of plasma replacement therapy, it is necessary to put the results of two recently published studies into routine clinical practice of continuous vein-venous HF (CVVHF) as soon as possible just in 2008. The performed studies suggest the most important role of adequate dosage of CVVHF and show that the use of a dose of 35 ml/kg/hr in critically ill patients with ARF increased survival by almost 20%. These two studies contain today's most vivid evidence, but one awaits the results of other studies that confirm (or do not confirm) these conclusions. In the world where more importance is attached to evidence-based medicine, two first-level studies will yield Stage A recommendations that may be guided by any intensive care specialist using CVVHF in expectation of the results of on-going investigations. Nevertheless, many difficulties are to be surmounted while introducing new procedures into routine intensive care practice. The most cardinal problems are those associated with requirements for blood flow via vascular access with pre- and postdilution procedures, with the type of employed membranes and substituting liquids, and with a possible need for concomitant dialysis. From the strictly practical standpoint, introduction of these changes into routine intensive care practice may be extremely difficult. This will undoubtedly require that physicians and nurses should make joint effects.

Acute kidney injury in the ICU: time has come for an early biomarker kit!

Early recognition of acute kidney injury (AKI) in the intensive care unit (ICU) remains a critical problem, with a rising incidence and a high mortality rate. As a consequence, the actual lack of an early and effective biomarker results in a significant delay in initiating appropriate therapy. The accurate diagnosis of AKI is especially problematic in critically-ill patients, in whom we know that renal function is in an unsteady state; therefore the validity of creatinine-based baseline assessment measures is reduced. Because the rationale for assessing AKI markers in critically-ill patients is strong at the present time, researchers are stimulated to establish a multidimensional AKI classification system. This system should in essence grade AKI severity. The most widely referenced classification is the RIFLE system. Thus, early recognition of AKI, well before changes in serum creatinine occur, has come under intensive research, because it is evidenced that even small increases in serum creatinine are associated with an increase in patient mortality. The development of a biomarker kit in which several early markers with different characteristics are combined, is essential. Multi-centre, randomized studies indicate a potential for early biomarkers able to diagnose AKI 48 hours before creatinine changes. In conclusion, time has come to leave serum creatinine behind as a marker of renal function in patients with AKI on the ICU. Only then will we be able to offer early goal-directed therapy for the kidney in the ICU setting.

The big bang of hemofiltration: the beginning of a new era in the third millennium for extra-corporeal blood purification!

Since the last decade, hemofiltration and especially high volume hemofiltration has rapidly evolved from a somewhat experimental treatment towards a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine resistant hypodynamic septic shock. Nevertheless, this approach lacks prospective randomized studies (PRT'S) evaluating the critical role of early hemofiltration in sepsis. An important step forward which could be called the 'big bang' in term of hemofiltration was the publication of a PRT in patients with acute renal failure (ARF) (1). Before this study (2), nobody believed that hemofiltration could change the survival rate in intensive care. Since that big bang, many physicians consider that hemofiltration at a certain dose can change the survival rate in intensive care. So the world of hemofiltration in ICU is not a definitive world, it is still in expansion. Indeed, we now have to try to define what will be the exact dose we need in septic acute renal failure. This dose might well be 'higher' than 35 ml/kg/hour in the septic acute renal failure 'group' as suggested by many studies (2-5). At present, it is the issue of continuous dose of high volume hemofiltration that has to be tested in future randomized studies. Since the Vicenza study (2) has shown that 35 ml/kg/h is the best dose in terms of survival, dealing with non septic acute renal failure in ICU, several studies from different groups have shown that, in septic acute renal failure, a higher dose might correlate with better survival. This has also been shown in some way by the study of the 'Vicenza group' but not with a statistically significant value (2). New PRT'S have just started in Europe like the IVOIRE study (hIgh VOlume in Intensive caRE) (6) and the RENAL study. Another large study is looking more basically at dose in non septic acute renal failure in Australasia and is led by the group of Rinaldo Bellomo in Melbourne (7) as well as the ATN study (8) led by Palevsky and colleagues in the USA, also testing the importance of dose in the treatment for ARF. Nevertheless, 'early goal-directed hemofiltration therapy' like early goal directed therapy (9) has to be studied in our critical ill patients. Regarding this issue, fewer studies, mainly retrospective exist, but again the IVOIRE study (6) will address this issue by studying septic patients with acute renal injury according to the Rifle classification (10). So, this review focuses on the early application and on the adequate dose of continuous high volume hemofiltration in septic shock in order to improve not only hemodynamics, but survival in this very severely ill cohort of patients. This could well be called the 'big bang of hemofiltration' as one could never have anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of ICU-septic acute renal failure patients. On top of the use of early and adequate dose of hemofiltration in sepsis, a higher dose could also provide better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this paper also reviews 'brand' new theories regarding the rationale for hemofiltration in sepsis. Finally, this paper also addresses the so-called negative studies as well anticipated side effects.

The "French Hemodiafe Trial": this study is neither decisive nor definitive in resolving the controversy on renal replacement therapy in ICU.

This short review paper addresses a recently published study on the controversy concerning the type of renal replacement therapy (RRT) used in ICU. It proposes a somewhat different point of view regarding this study, based on the numerous problems that have been identified with it. Indeed, given these shortcomings, the study conclusions are somewhat misleading and are not effectively supported by the trial data. If the treatment doses were comparable and kept constant in the OIHDO group, then the results may well have been strikingly different. In keeping with all drugs used in medicine, dose is crucial and should have remained unchanged by the investigators during the study in order to be able to draw valid conclusions based on the evidence. There is a need for a further study comparing CRRT and IHD. This should be better designed in terms of the exclusion criteria, delivered dose of CVVH (35 ml/kg/h) and IHD, timing of treatment and should also examine more secondary endpoints. This may answer many of the outstanding issues and provide a balanced opinion about this study and its real importance in ICU practice. Finally, this study does not have the scientific power (as explained by the accompanying editorial by Kellum) to put an end to the ICU controversy regarding the choice of RRT in acute renal failure while in ICU. Therefore, there is an urgent need for a better designed study regarding this controversy.

[Comparison of eight deep breaths and tidal volume breathing preoxygenation techniques in morbid obese patients]. / Comparaison de la technique de préoxygénation à huit capacités vitales et à volume courant chez les patientes ayant une obésité morbide.

OBJECTIVE: To compare two techniques of preoxygenation, eight deep breaths (8DB) and tidal volume breathing in obese patients by measuring end-tidal fractional oxygen concentration (FETO2) and apnea time from 100% of hemoglobin saturation to 95% (T95%). STUDY DESIGN: Prospective randomized study. METHODS: Twenty obese patients (BMI >40 kg/m2) without cardiorespiratory disease nor difficult intubation criteria were randomized into two groups of ten. One group received preoxygenation with eight deep breaths in one minute (8DB) and the other with three minutes tidal volume preoxygenation (3TV) both under FIO2 100%. FETO2 every minute of preoxygenation and T95% were measured. Data were analyzed with Mann and Whitney test. A p <0.05 was considered significant. RESULT: There was no significant difference between the groups regarding FETO2 values [84 +/- 4% (8DB) and 88 +/- 5% (3TV)] and T95% [176 +/- 23 s (8DB) and 181 +/- 35 s (3TV)]. The PETCO2 was significantly inferior in the 8DB group at the end of preoxygenation [PETCO2 =29 +/- 1 mmHg (8DB) and PETCO2 =36 +/- 5 mmHg (3TV)]. CONCLUSION: 8DB and 3TV preoxygenation techniques in morbid obese patients induce similar FETO2 and T95%. However hyperventilation effects in the 8DB group are unknown.