Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration: PROSPERO Identifier: CRD42021230155.

Perioperative goal-directed hemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery).

BACKGROUND: In this study, our objective was to determine whether a perioperative hemodynamic protocol based on noninvasive cardiac output monitoring decreases the incidence of postoperative complications and hospital length of stay in major abdominal surgery patients requiring intensive care unit admission. Secondary objectives were the time to peristalsis recovery and the incidence of wound infection, anastomotic leaks, and mortality. METHODS: A randomized clinical trial was conducted in 6 tertiary hospitals. One hundred forty-two adult patients scheduled for open colorectal surgery, gastrectomy, or small bowel resection were enrolled. A hemodynamic protocol including fluid administration and vasoactive drugs based on arterial blood pressure, cardiac index, and stroke volume response was compared with standard practice. Patients were followed until hospital discharge (determined by a surgeon blinded to the study) or death. In contrast to previous studies, we designed a pragmatic trial (as opposed to explanatory trials) to mimic real practice and obtain maximal external validity for the study. RESULTS: Fluid administration was similar except for the number of colloid boluses (2.4 ± 1.8 [treated] vs 1.3 ± 1.4 [control]; P < 0.001) and packed red blood cell units (0.6 ± 1.3 [treated] vs 0.2 ± 0.6 [control]; P = 0.019). Dobutamine was used in 25% (intraoperatively) and 19.4% (postoperatively) of the treated patients versus 1.4% and 0% in the control group (P < 0.001). We have observed a reduction in reoperations in the treated group (5.6% vs 15.7%; P = 0.049). However, no significant differences were observed in overall complications (40% vs 41%; relative risk 0.99 [0.67-1.44]; P = 0.397), length of stay (11.5 [8-15] vs 10.5 [8-16]; P = 0.874), time to first flatus (62 hours [40-76] vs 72 hours [48-96]; P = 0.180), wound infection (7 vs 14; P = 0.085), anastomotic leaks (2 vs 5; P = 0.23), or mortality (4.2% vs 5.7%; P = 0.67). CONCLUSIONS: The results of our pragmatic study indicate that a perioperative hemodynamic protocol guided by a noninvasive cardiac output monitor was not associated with a decrease in the incidence of overall complications or length of stay in major abdominal surgery.

Pre-intubation ventilation device for bearded patients: prospective, randomized, crossover trial in anesthetized patients.

Having a beard is an independent predictor of difficult ventilation by face mask. This study evaluates the efficacy of a novel intra-oral Bag-Valve-Guedel Adaptor (BVGA) in anaesthetized bearded patients. Patients with ASA score 1-2, scheduled for elective surgery, were recruited for this prospective, crossover trial. Beard length was categorized as < 0.5 cm, 0.5-1 cm, 1-5 cm, or > 5 cm. Patients were ventilated by attending anesthesiologists using the BVGA and a facemask (both with a Guedel oral airway). End-tidal CO2 (EtCO2) and expiratory tidal volume (TV) were recorded as was the number of hands required for the procedure. The primary outcome was the difference between BVGA and Facemask. Sixty-one patients were enrolled. Of these, 38 had beards, and 23 were without beards or with beards < 0.5 cm length. In bearded patients, ventilation with the BVGA was superior to the face mask by EtCO2 and non-inferior by TV (BVGA-vs-Mask, mean [95% CI]: EtCO2 [mmHg], 33.0 [31.6, 34.3]-vs-27.2 [25.5, 28.8], p < 0.001; TV [ml∙kg-1 IBW], 8.1 [7.4, 8.9]-vs-6.9 [6.0, 7.7], p = 0.11). The BVGA was found to be superior to the face mask by EtCO2 across all beard lengths (p ≤ 0.001), but by TV only for the longest beard group (p = 0.009). After securing the BVGA, ventilation was possible without hands in 74% of the cases - clearly impossible with the facemask (p ≤ 0.001). The BVGA is more effective and more convenient than the facemask in anaesthetized bearded patients. A follow-up study is underway to test whether replacing the face mask with the BVGA will improve effectiveness and ease of pre-intubation field ventilation by less-experienced, first responders.

Outcome predictors and patient progress following delivery in pregnant and postpartum patients with severe COVID-19 pneumonitis in intensive care units in Israel (OB-COVICU): a nationwide cohort study.

BACKGROUND: A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery. METHODS: In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery). FINDINGS: From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO2), SpO2 to fraction of inspired oxygen (FiO2) ratio (S/F ratio), partial pressure of arterial oxygen to FiO2 ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores. INTERPRETATION: In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation. FUNDING: None.

Arterial and plethysmographic waveform analysis in anesthetized patients with hypovolemia.

BACKGROUND: Respiratory-induced arterial and plethysmographic (pulse oximetry) waveform changes were shown to be good predictors of cardiac output response to increased preload. The aim of this study was to evaluate the reliability of arterial and plethysmographic waveform variables in patients with mild hypovolemia. METHODS: Patients undergoing autologous hemodilution were studied. After anesthesia induction, hemodilution was performed by withdrawing blood in steps of 2% of estimated circulating blood volume (ECBV), up to 20%. The patients who did not develop hypotension (systolic blood pressure < 80 mmHg) were studied. Arterial and plethysmographic waveforms were recorded and analyzed off-line at baseline and after each withdrawal of blood. Variations in arterial systolic and pulse pressure were analyzed using standard methods. Plethysmographic waveform variation and delta pulse oximetry plethysmography were determined by using pulse oximetry recordings. RESULTS: There were 33 study participants. Systolic blood pressure decreased by 11%, and heart rate increased from 73 to 76 beats/min after a 20% reduction of ECBV. Systolic pressure and pulse pressure variations increased (P < 0.005) after a 4% reduction of ECBV. The values of arterial pressure and pulse oximetry waveform variables almost doubled in value after a 20% reduction of ECBV. Systolic pressure variation was the most reliable variable during hypovolemia. Plethysmographic waveform variation increased significantly after a 6% reduction of ECBV and delta pulse oximetry plethysmography after an 8% reduction of ECBV. CONCLUSIONS: Arterial and pulse oximetry respiratory-induced changes in waveform variables are reliable indicators of mild hypovolemia in anesthetized patients. The pulse oximetry plethysmographic waveforms accurately reflect arterial waveforms during more progressive hypovolemia.

Remifentanil versus fentanyl for esophagogastroduodenoscopy in children.

OBJECTIVES: We compared sedation by propofol combined with either fentanyl or remifentanil in pediatric outpatients undergoing diagnostic esophagogastroduodenoscopy. PATIENTS AND METHODS: Forty-two children scheduled for esophagogastroduodenoscopy in our institution were randomly assigned to receive 2 mg/kg propofol plus either 1 µg/kg bolus of fentanyl (group F; n = 20) or 0.5 µg/kg bolus of remifentanil (group R; n = 22). Cardiorespiratory parameters, sedation level, adverse effects related to the drugs and/or to the procedure, ease of performance for the endoscopist, and time to awakening were analyzed. RESULTS: There were no clinically significant changes in hemodynamics. Apnea periods >20 seconds and decreases in SaO2 <90% occurred more frequently in group R (31.8% vs 0%, P < 0.01, and 27.3% vs 5.0%, P > 0.05, respectively). Children in group R had significantly shorter average time to awakening: 9.5 ± 5.6 vs 16.5 ± 10.5 minutes (P = 0.01), and received a significantly lower total dose of propofol (P = 0.034). Adverse effects within the first 24 hours postprocedure occurred less frequently in group R (P = 0.03). CONCLUSIONS: Remifentanil in combination with propofol provides good analgesic and sedative effects, which were shorter lasting compared with fentanyl-based sedation, and caused fewer delayed adverse effects. The use of remifentanil was associated with respiratory depression, emphasizing the need for experienced anesthesiologists.

Platelet function recovery after cessation of aspirin: preliminary study of volunteers and surgical patients.

BACKGROUND AND OBJECTIVE: Recent evidence indicates that platelet function may recover more rapidly after cessation of aspirin therapy than previously thought. The present study evaluated the effect of aspirin on platelet function using platelet aggregometry in healthy individuals and in aspirin-treated patients scheduled for surgery. METHODS: Platelet aggregation in response to arachidonic acid, epinephrine, and adenosine diphosphate was determined in 14 male volunteers during and after 10 days' aspirin administration (100 mg) and in 58 aspirin-treated patients during intake, on days 3, 4 or 6 after drug cessation, and on day 10 after drug cessation, prior to elective surgery. Urine thromboxane (11-dehydro-thromboxane B2) concentrations were also measured. RESULTS: Platelet aggregation in response to arachidonic acid and epinephrine was significantly decreased in both volunteers and patients during aspirin administration. The aggregation normalized within 3 days of aspirin cessation in the volunteers and within 4-6 days in the patients. Urine concentration of 11-dehydro-thromboxane B2 was about three times lower with aspirin treatment than without, although in two patients concentrations were higher with aspirin. CONCLUSION: Platelet aggregometry with arachidonic acid is a sensitive test for the evaluation of the effects of aspirin on platelet function. In most aspirin-treated patients, platelet function recovers 4 days after drug cessation, although the process is sometimes prolonged. Therefore, the time of aspirin cessation before scheduled surgery should be determined individually.

The impact of an electronic reminder on the use of alarms after separation from cardiopulmonary bypass.

INTRODUCTION: During cardiopulmonary bypass (CPB) monitor alarms are routinely disabled. Failure to reactivate these alarms after CPB may jeopardize patient safety. We have produced an electronic reminder that automatically alerts clinicians to reactivate alarms after CPB and have evaluated the alarm reactivation rate after its implementation. METHODS: We developed and implemented an algorithm that identifies separation from CPB by the return of pulsatile flow and of mechanical ventilation, and checks alarm status (activated, disabled or silenced). If alarms have not been reactivated after separation from CPB, an electronic reminder appears. Data were collected during three time periods: Stage I (304 patients)--baseline period before implementation of the electronic reminder; Stage II (256 patients)--after implementation; Stage III-(435 patients) after a single educational departmental meeting, at the end of Stage II. Incidence of proper alarm reactivation and the number of electronic reminders per patient were compared among stages. RESULTS: The rate of alarm reactivation at baseline (Stage I) was 22%, increased to 63% (Stage II), and again to 83% during Stage III (P < 0.001). The spontaneous alarm reactivation rate before the appearance of the electronic reminder on the anesthesia information management system screen increased from 19% at Stage II to 42% at stage III (P < 0.001). CONCLUSION: Introducing an automatic electronic reminder significantly increased the rate of alarm reactivation after separation from CPB. Real-time computerized decision-support tools can be developed within anesthesia information management system and may be useful for improving safety during anesthesia.

The effect of acute autologous blood transfusion on coagulation dysfunction after cardiopulmonary bypass.

OBJECTIVE: To evaluate the influence of acute autologous blood transfusion on postcardiopulmonary bypass coagulation disturbances evaluated by thromboelastography (TEG) as a point-of-care test. METHODS: This prospective randomized controlled study included consecutive patients who underwent elective cardiac surgery with cardiopulmonary bypass. The patients in group A underwent acute autologous blood transfusion with acute normovolemic haemodilution and those in group H received homologous blood, if needed, and served as controls. RESULTS: A total of 62 patients, from 68 enrolled, completed the study: 27 in group A and 35 in group H. Both groups had similar prolongation of prothrombin time and partial thromboplastin time, decreased platelets count and changes in postoperative thromboelastographic variables. There were no differences between them for postoperative bleeding, blood transfusions or haemoglobin values. There was significant prolongation of the R value of TEG (without heparinase) in both groups at 4 h after surgery compared with the immediate postoperative values: from 11.3 +/- 4.2 to 12.3 +/- 5.5 mm, P < 0.05 for group A and from 9.9 +/- 3.7 to 12.5 +/- 5.4 mm, P < 0.01 for group H. The R values of TEG with and without heparinase differed significantly (P < 0.05) at 4 h postoperatively. CONCLUSION: Autologous blood transfusion of 15% estimated blood volume did not affect postcardiopulmonary bypass coagulopathy, nor did it decrease blood loss or homologous blood and its products transfusion in the early postoperative period. TEG is a valuable measure for detecting coagulation dysfunction with a potential role in the postoperative management of cardiac patients.

The Israeli anesthesiology physician workforce.

BACKGROUND: Anesthesiology is a vital specialty that permits the safe and humane performance of painful procedures. Most Israeli anesthesiologists are immigrants, while only a minimal number of Israeli medical school graduates enter the specialty. Unfortunately, the supply of immigrant physicians is declining due to falling immigration rates. OBJECTIVES: To examine the current Israeli anesthesiology workforce and project future needs. METHODS: Demographic and professional information about Israeli hospital anesthesiologists was solicited from anesthesiology department heads. Data were also gathered about the past, present and projected future growth, age distribution and birth rate of the Israeli population. Needs and demand-based analyses were used to project future anesthesiology workforce requirements. RESULTS: Data on 711 anesthesiologists were obtained from 30 hospital anesthesiology department heads. Eighty-seven anesthesiologists (12.2%) graduated from Israeli medical schools and 459 (64.6%) graduated from medical schools in the former Soviet Union. Among the 154 anesthesiology residents < or = 40 years old, only 13 (8.4%) graduated from Israeli medical schools. There are approximately 10.8 anesthesiologists per 100,000 population. Projections for 2005-2015 revealed a need for 250-300 new anesthesiologists. CONCLUSIONS: The anesthesiology workforce is predominantly composed of immigrants. This has vast implications for the future viability of the specialty because of the continuing reduction in immigration, the lack of interest in the specialty by Israeli medical school graduates, and the projected need for many new anesthesiologists to replace retirees and to provide care to a growing and aging population.

Can external signs of trauma guide management?: Lessons learned from suicide bombing attacks in Israel.

BACKGROUND: Following a suicide bombing attack, scores of victims suffering from a combination of blast injury, penetrating injury, and burns are brought to local hospitals. OBJECTIVE: To identify external signs of trauma that would assist medical crews in recognizing blast lung injury (BLI) and effectively triaging salvageable and nonsalvageable victims. DESIGN: Retrospective analysis of all 15 suicide bombing attacks that occurred in Israel from April 1994 to August 1997. SETTING: National survey. PATIENTS: One hundred fifty-three victims died and 798 were injured as a result of 15 attacks. Medical records were reviewed for external signs of trauma, such as burns and penetrating injuries, and the presence of BLI. Main Outcome Measure The odds ratio for BLI and death. RESULTS: Three settings were targeted: buses, semiconfined spaces, and open spaces. Sixty survivors (7.5%) suffered from BLI, which was more common in buses (37 of 260) than semiconfined spaces (14 of 279) and open spaces (9 of 259) (P<.001). Victims with BLI were more likely to suffer from penetrating injury to the head or torso, burns covering more than 10% of the body surface area, and skull fractures (odds ratios, 4, 11.6, and 55.8, respectively; P<.001). Victims who died at the scene were more likely to suffer from burns, open fractures, and amputations in comparison with survivors (odds ratios, 6.5, 18.6, and 50.1, respectively; P<.001). CONCLUSIONS: Following a suicide bombing attack, external signs of trauma should be used to triage victims to the appropriate level of care both at the scene and in the hospital. Triage of salvageable and nonsalvageable victims should take into account the presence of amputations, burns, and open fractures.

Evaluation of changes in forgoing life-sustaining treatment in Israeli ICU patients.

INTRODUCTION: Over the last several years, there have been legal decisions and changes in medical directives concerning end-of-life decisions in Israel. METHODS: The data were compared to evaluate the changes in the frequency and types of forgoing of life-sustaining treatment (FLST) in patients who were admitted to the ICU during period I (November 1994 to July 1995) and period II (January 1998 to January 1999). RESULTS: During period I, there were 385 ICU admissions, and during period II there were 627 ICU admissions. In period I, FLST or death occurred in 13.5% of patients, and in 12% in period II. There was no significant difference in cardiopulmonary resuscitation (9% vs 13%, respectively), withholding therapy (90% vs 91%, respectively), or withdrawing therapy (0% vs 0%, respectively) between the two study periods. CONCLUSIONS: There was no significant change in the frequency or types of FLST in an Israeli ICU between 1994 and 1998, despite passage of a new Patients' Rights Law and the issuing of a Ministry of Health directive on the treatment of the terminally ill, both of which occurred in 1996, and recent district court decisions favoring the termination of life-sustaining therapies.

End-of-life intensive care unit decisions, communication, and documentation: an evaluation of physician training.

PURPOSE: The majority of patients dying in intensive care units (ICUs) do so after the forgoing of life-sustaining therapies (FLST). Communication between physicians, patients, and their families regarding the decision to FLST has not been evaluated in Israel. MATERIALS AND METHODS: All patients who had FLST in a general ICU were enrolled in the study. We evaluated whether physicians communicated and documented the FLST decisions with patients or the patients' families. We also assessed the effect of the physician's geographic place of training on communication behavior. RESULTS: Over a period of 8.5 months, 385 patients were admitted to a general ICU in Israel. Fifty-seven patients died or had FLST. Twelve of these 57 were excluded from the study. Thus, 45 (79%) patients had FLST and were enrolled in the study. All patients were deemed medically incompetent to make FLST decisions. In 24 (53%) patients, FLST was discussed with the family before the decision to forgo therapy. Discussion occurred later with 6 other families, who were unavailable at the time the FLST decision was made. In 15 patients, there were no discussions with families. American-trained physicians discussed FLST with 22 of 29 families initially and 5 other families later (93%), whereas the Eastern European-trained physicians discussed FLST with only 3 of 16 (19%) families (P <.001). Documentation of FLST was present in 26 (90%) patients of American-trained physicians and 8 (50%) patients of Eastern European-trained physicians (P <.001). CONCLUSIONS: FLST is common in an Israeli ICU. Patients are not medically competent to make FLST decisions. American-trained physicians discuss and document FLST more often than Eastern European-trained physicians.

Pressure-related hemodynamic effects of CO2 pneumoperitoneum in a model of acute cardiac failure.

BACKGROUND: The adverse effects related to CO2 pneumoperitoneum (PP) have been well documented. Although these effects in the state of cardiac failure have not been investigated, it appears to be common current clinical practice to use low-pressure PP in this clinical setting, assuming it to be safer. OBJECTIVE: The aim of our study was to compare the hemodynamic changes with the application of conventional 15 mm Hg PP versus low-pressure 10 mm Hg PP in control and acute cardiac failure (ACF) animal models. METHODS: We studied changes in cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR), applying 10 mm Hg and 15 mm Hg CO2 PP in control and, following the pharmacological induction of acute cardiac failure, in 10 domestic pigs. RESULTS: In control, the application of 10 mm Hg PP did not cause any significant hemodynamic changes compared to baseline parameters. The use of 15 mm Hg PP in the model with normal cardiac function, however, produced a significant change in the tested hemodynamic values: CO decreased from 3.8L/min to 2.8L/min (P =.0018); SV declined from 38 mL to 30 mL (P =.046); SVR increased from 1677 dyne.s.cm-5 to 2414 dyne.s.cm-5 (P =.049) compared to baseline. In the model of ACF induced by the intravenous infusion of sodium pentobarbital, the application of either 10 mm Hg or 15 mm Hg PP was found to have a similar hemodynamic trend: CO, 1.65 L/min vs. 1.41 L/min; SV, 23.2 L vs. 20.9 L; SVR, 2487 dyne.s.cm-5 vs. 2597 dyne.s.cm-5 (P = NS for all). CONCLUSIONS: The application of low-pressure 10 mm Hg PP, compared to conventional 15 mm Hg PP, in the animal model of ACF does not appear to have any hemodynamic advantages.

Respiratory variations in the arterial pressure during mechanical ventilation reflect volume status and fluid responsiveness.

Optimal fluid management is one of the main challenges in the care of the critically ill. However, the physiological parameters that are commonly monitored and used to guide fluid management are often inadequate and even misleading. From 1987 to 1989 we published four experimental studies which described a method for predicting the response of the cardiac output to fluid administration during mechanical ventilation. The method is based on the analysis of the variations in the arterial pressure in response to a mechanical breath, which serves as a repetitive hemodynamic challenge. Our studies showed that the systolic pressure variation and its components are able to reflect even small changes in the circulating blood volume. Moreover, these dynamic parameters provide information about the slope of the left ventricular function curve, and therefore predict the response to fluid administration better than static preload parameters. Many new dynamic parameters have been introduced since then, including the pulse pressure (PPV) and stroke volume (SVV) variations, and various echocardiographic and other parameters. Though seemingly different, all these parameters are based on measuring the response to a predefined preload-modifying maneuver. The clinical usefulness of these 'dynamic' parameters is limited by many confounding factors, the recognition of which is absolutely necessary for their proper use. With more than 20 years of hindsight we believe that our early studies helped pave the way for the recognition that fluid administration should ideally be preceded by the assessment of "fluid responsiveness". The introduction of dynamic parameters into clinical practice can therefore be viewed as a significant step towards a more rational approach to fluid management.