Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients

Background  

Red blood cell (RBC) transfusion is commonly used to increase oxygen transport in patients with sepsis. However it does not consistently increase oxygen uptake at either the whole-body level, as calculated by the Fick method, or within individual organs, as assessed by gastric intra-mucosal pH.     

Yersinia septic shock following an autologous transfusion in a pediatric patient.

Although the literature on infections transmitted via transfused blood focuses on viruses, Yersinia enterocolitica can also cause severe infections in patients receiving transfusions. A 13-year-old patient developed severe sepsis after an autologous blood transfusion contaminated with Y. enterocolitica. The patient was an otherwise healthy female undergoing posterior spinal fusion for congenital scoliosis. Prior to surgery, the patient donated blood for perioperative and postoperative use. A few days before the donation, she had complained of abdominal pain and was experiencing mild diarrhea. The patient received four units of packed red blood cells (PRBCs) during the surgery. Intraoperatively, the patient developed fever up to 103.6 degrees F, became hypotensive requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. The surgery team believed the patient was experiencing malignant hyperthermia and attempted to cool patient during the procedure. Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock of unknown etiology. The patient further developed disseminated intravascular coagulation. The patient received supportive care and was started on ampicillin/sulbactam on postoperative day (POD) one which was changed to clindamycin, ciprofloxacin and tobramycin on POD two when blood cultures grew gram-negative bacilli. On POD three, cultures were identified as Y. enterocolitica and antibiotics were changed to tobramycin and cefotaxime based on susceptibility data. Sequelae of the shock included adult respiratory distress syndrome requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required a bilateral below the knee amputation. The cultures of the snippets from the bags of blood transfused to the patient also grew Y. enterocolitica. This case illustrates the importance of considering transfusion related bacterial infections in patients receiving PRBCs. All patients in shock following any type of transfusion may require aggressive antibiotic therapy, until the diagnosis and etiology are known.     

Absence of supply dependence of oxygen consumption in patients with septic shock

We tested whether oxygen consumption ( o₂) was dependent on oxygen delivery ( o₂) in 10 patients with septic shock when o₂ was changed by the use of the inotropic agent, dobutamine. The mean acute physiology and chronic health evaluation (APACHE) II score of the patients was 27.3 ± 8.1 with a mean blood pressure on entry of 66.8 ± 12.4 mm Hg, and all had been volume resuscitated to a pulmonary artery occlusion pressure of greater than 10 mm Hg. We measured o₂ by analysis of respiratory gases NOW) while calculating o₂ by the Fick equation NOV) at three different OZ deliveries. When the dobutamine infusion rate was increased from 2.5 ± 4.0 to 12.3 ± 6.0 μg/kg/min, thermodilution cardiac output increased from 7.7 ± 2.6 to 10.1 ± 2.7 L/min (P < .01). Accordingly, dobutamine increased o₂ from 13.5 ± 3.8 to 18.2 ± 4.3 mL/min per kg (increase of 36.4% ± 19.7%; P < .01), but o_2G did not increase (3.2 ± 0.5 to 3.2 ± 0.6 mL/ min per kg). During these same interventions, the o_2F tended to increase (2.9 ± 0.7 to 3.4 ± 0.8 mL/min per kg, P < .06), presumably a spurious correlation because of measurement errors shared by the calculation of o_2F and o₂. Neither lactic acidosis nor acute respiratory distress syndrome (ARDS) conferred supply dependence of o_2G, but the presence of ARDS was predictive of death in this cohort. It is concluded that o₂ is independent of o₂ in patients with septic shock and lactic acidosis. These data confirm that maximizing o₂ beyond values achieved by initial fluid and vasoactive drug resuscitation of septic shock does not improve tissue oxygenation as determined by respiratory gas measurement of o₂.     

The effects of norepinephrine infusion on oxygen consumption in a patient with septic shock

A 65-year-old man developed postsurgical septic shock, unresponsive to plasma volume expansion and administration of dopamine and dobutamine. A continuous norepinephrine infusion was then started and the dose increased to 0.62 g·kg^–1·min^–1 until the mean arterial pressure was 70 mmHg. Prior to and during the norepinephrine infusion, oxygen consumption was continuously measured with a mass spectrometer system. There was a parallel increase in mean arterial pressure and oxygen consumption (+35%). There was also an increase in cardiac index and oxygen delivery. Systemic vascular resistance was only transiently increased. In this case with septic shock, norepinephrine infusion improved hemodynamic variables with an associated increase in oxygen consumption.     

脓毒性休克时大鼠全身氧供给与氧消耗关系的变化

目的：观察脓毒性休克时全身氧供给（ＤＯ２）与氧消耗（ＶＯ２）关系的变化。方法：以改良的盲肠结扎穿孔（ＣＬＰ）方法制备大鼠脓毒性休克模型，观察大鼠休克过程中ＤＯ２、ＶＯ２、氧摄取率（ＥＲＯ２）等变化。结果：ＣＬＰ后５小时已出现平均动脉压明显下降（Ｐ＜０．０５）。在休克早期，ＤＯ２即进行性下降，ＥＲＯ２出现代偿性升高，ＶＯ２维持相对不变，呈非氧供依赖关系；当ＤＯ２降至３４．６０ｍｌ·ｋｇ－１／ｍｉｎ后，ＶＯ２随ＤＯ２线性降低（ｒ＝０．７３３，Ｐ＜０．０１），即呈病理性氧供依赖关系。结论：脓毒性休克时ＤＯ２与ＶＯ２间呈双相变化关系，病理性氧供依赖的出现与组织氧摄取和氧利用功能障碍有关。     

容量状态对革兰氏阴性杆菌感染性休克患者血液动力学类型及氧代谢的影响

目的　探讨容量状态对感染性休克患者血液动力学状态及氧化谢的影响。方法　监测10例感染性休克患者不同容量状态下血液动力学及氧化谢的变化。结果　低血容量时,肺动脉嵌压(PAWP)0.8±0.3kPa,心脏指数(CI)2.0±0.4L     

Early blood lactate area as a prognostic marker in pediatric septic shock

Purpose

We attempted to evaluate whether the early lactate area is useful as an early prognostic marker of mortality in pediatric septic shock patients.

Methods

We performed a retrospective study of pediatric patients with septic shock who were admitted to the pediatric intensive care unit of Asan Medical Center, Seoul, Korea. Serial arterial lactate levels were obtained immediately and then every 6 h after admission for a total of 24 h. The lactate area (mmol/lh) was defined as the sum of the area under the curve (AUC) of serial lactate levels measured during the 24 h following admission. We compared the lactate-associated parameters as a predictor of mortality.

Results

A total of 65 patients were included in this study, and the overall 28-day mortality of these patients was 26.2 %. Survivors compared with non-survivors had an initial lactate level of 3.13 ± 2.79 vs. 6.16 ± 4.87 mmol/l, a lactate clearance of 32.8 ± 63.4 vs. ?30.8 ± 75.6 %, and a lactate area of 59.7 ± 56.0 vs. 168.0 ± 107.0 mmol/lh (p < 0.05 for all variables). Receiver operating characteristic curves indicated a strong predictive power for the lactate area (AUC = 0.828), which demonstrated the largest AUC in comparison with the AUCs of the initial lactate level (0.699) or the 24-h lactate clearance (0.719). Using multivariate logistic regression analysis, the lactate area was a significant prognostic factor.

Conclusion

The early lactate area is a potentially feasible and clinically useful predictor of mortality in pediatric septic shock patients.     

Oxygen consumption in sepsis and septic shock

This review article examines the pathophysiology of septic shock, with special attention to the concept of supply-dependent consumption and the implications this concept has for therapy. Patients with septic shock require higher levels of oxygen delivery (DO2) to maintain aerobic metabolism. When DO2 is inadequate, peripheral tissues switch to anaerobic metabolism and oxygen consumption decreases. The lactic acidosis that occurs is a reasonable clinical marker of supply dependency and inadequate tissue perfusion. Maximizing DO2 is an important part of the hemodynamic resuscitation of patients with septic shock. To achieve this goal, intravascular volume must be restored and the myocardial depression associated with sepsis must be treated to optimize cardiac output. The normalization of arterial lactate concentration is a reasonable goal of resuscitative efforts.     

Markers of tissue hypoperfusion in pediatric septic shock

Objective: To describe measurements of global oxygenation parameters, markers of splanchnic hypoperfusion and those of metabolic activity related to cellular energy production among critically ill children with septic shock.¶Design: Clinical study of a series of cases.¶Patients and participants: 11 previously healthy children with septic shock admitted to the pediatric intensive care unit (ICU) of a university hospital.¶Interventions: None.¶Measurements and results: Oxygen consumption, oxygen delivery (DO₂), serum bicarbonate, arterial pH, gastric intramucosal pH (pHi), gastroarterial carbon dioxide tension gradient, serum lactate, pyruvate, lactate to pyruvate ratio (L/P), ketone body ratio, and the esterified to free carnitine ratio were measured serially at 0, 6, 12, 24, 36, and 48 h after admission to the pediatric ICU. All children survived. One patient failed to show supranormal DO₂ ( > 570 ml/min per m²). Normalization of serum bicarbonate and lactate were associated with patient recovery. One patient presented an increasingly abnormal L/P ratio with normal lactate levels, suggesting an increased utilization of pyruvate rather than an increased cytosolic redox potential. Although values of gastric pHi < 7.30 were observed in 43 % of samples, serial measurements in individuals showed significant variability and unpredictable trends. Free fatty acid concentrations, ketone body production, and carnitine levels remained within the normal range.¶Conclusions: In this study, trends in serum bicarbonate and lactate somewhat characterized the recovery of children with septic shock. Based on our data, it is unclear how other markers may have been used to modify therapy.     

Impact of red blood cell transfusion on regional cerebral oxygen saturation during pediatric ECMO

Background

Low cerebral regional tissue oxygenation (crSO2) is associated with unfavorable neurological outcomes in children requiring extracorporeal membrane oxygenation (ECMO) support. Red blood cell (RBC) transfusion can improve brain oxygenation and crSO2 has been proposed as a noninvasive monitoring tool that could aid in RBC transfusion decision-making. However, how crSO2 responds to RBC transfusion is largely unknown.

Study Design and Methods

This was a retrospective, observational cohort study of all patients <21 years supported on ECMO at a single institution from 2011 to 2018. Transfusion events were grouped by pre-transfusion hemoglobin concentration (<10, 10- < 12, and ≥ 12 g/dL). Post- versus pre-transfusion crSO2 changes were analyzed using linear mixed-effects models.

Results

The final cohort included 830 transfusion events in 111 patients. Hemoglobin increased significantly post- versus pre-RBC transfusion (estimated mean increase of 0.47 g/dL [95% CI, 0.35–0.58], p < .001), as did crSO2 (estimated mean increase of 1.82 percentage points [95% CI, 1.23–2.40], p < .001). Larger improvements in crSO2 were associated with lower pre-transfusion crSO2 values (p < .001). There was no difference in mean change in crSO2 across the three hemoglobin groups in unadjusted analysis (p = .5) or after adjusting for age, diagnostic category, and pre-transfusion rSO2 (p = .15). Pre-transfusion crSO2 was <50% for 112 of 830 (13.5%) transfusion events, with only 30 (26.8%) crSO2 measurements noted to increase ≥50% post-transfusion.

Discussion

Among neonatal and pediatric patients on ECMO support, there was a statistically significant increase in crSO2 following RBC transfusion, although clinical significance needs to be investigated further. The effect was strongest among patients with lower crSO2 pre-transfusion.     

Biomarkers for pediatric sepsis and septic shock

Sepsis is a clinical syndrome defined by physiologic changes indicative of systemic inflammation, which are likely attributable to documented or suspected infection. Septic shock is the progression of those physiologic changes to the extent that delivery of oxygen and metabolic substrate to tissues is compromised. Biomarkers have the potential to diagnose, monitor, stratify and predict outcome in these syndromes. C-reactive protein is elevated in inflammatory and infectious conditions and has long been used as a biomarker indicating infection. Procalcitonin has more recently been shown to better distinguish infection from inflammation. Newer candidate biomarkers for infection include IL-18 and CD64. Lactate facilitates the diagnosis of septic shock and the monitoring of its progression. Multiple stratification biomarkers based on genome-wide expression profiling are under active investigation and present exciting future possibilities.     

Conjunctival oxygen tension monitoring in experimental septic shock

Continuous non-invasive monitoring of conjunctival oxygen tension (PcjO₂) versus conventional invasive hemodynamic and oxygen transport variables was evaluated in a porcine model of septic shock induced by a continuous i.v. infusion of E.coli endotoxin over 2 hours. Seventeen pigs under ketamine anesthesia and breathing air spontaneously were investigated. PcjO₂, which reflects local oxygen tension at tissue level, correlated significantly at baseline and throughout the septic course with mixed venous oxygen saturation and oxygen utilization coefficient. All these correlations were significant at the 1% level. The corresponding correlations between PcjO₂ and cardiac output were significant at the 5% level. A finding of great importance was that changes in PcjO₂ preceded major changes in the intermittently measured physiological variables such as SvO₂ and cardiac output.We conclude that PcjO₂ monitoring is a valuable non-invasive method and which can provide a continuous assessment of the hemodynamic and oxygenation status in experimental septic shock.     

Blood transfusion and oxygen consumption in surgical sepsis

OBJECTIVE: To evaluate the use of serum lactic acid values to predict flow-dependent increases in oxygen consumption (VO2) in response to increasing oxygen delivery (DO2) after blood transfusion in surgical sepsis. DESIGN: Prospective study. SETTING: Tertiary care, trauma center. PATIENTS: Twenty-one patients, postsurgical or posttrauma, judged septic by defined criteria. INTERVENTIONS: Serum lactic acid concentrations, DO2, and VO2 were measured before and after transfusion therapy. MEASUREMENTS AND MAIN RESULTS: Overall, the DO2 increased from 532 +/- 146 to 634 +/- 225 (SD) mL/min.m2 (p less than .001), and the VO2 increased from 145 +/- 39 to 160 +/- 56 mL/min.m2 (p = .02). These changes occurred with an Hgb increase from 9.3 +/- 1.1 to 10.7 +/- 1.5 g/dL (p less than .001). The patients were grouped by their pretransfusion serum lactic acid values. In those patients with normal (less than 1.6 mmol/dL) serum lactic acid (n = 10), DO2 increased from 560 +/- 113 to 676 +/- 178 mL/min.m2 (p less than .02), and VO2 increased from 150 +/- 25 to 183 +/- 46 mL/min.m2 (p less than .02). However, in the increased serum lactic acid group (n = 17), VO2 was not significantly changed after transfusion (143 +/- 46 to 146 +/- 58 mL/min.m2) despite increased DO2 (515 +/- 163 to 609 +/- 251 mL/min.m2, p less than .01). CONCLUSIONS: Blood transfusion can be used to augment DO2 and VO2 in septic surgical patients. Increased serum lactic acid values do not predict patients who will respond. The absence of lactic acidosis should not be used in this patient population to justify withholding blood transfusions to improve flow-dependent VO2. Patients who have increased lactate concentrations may have a peripheral oxygen utilization defect that prevents improvement in VO2 with increasing DO2.     

Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine

OBJECTIVES: To measure changes in medullary and cortical renal blood flow during experimental hyperdynamic sepsis and the effect of subsequent norepinephrine infusion on such flows.DESIGN Experimental animal study. SETTING: Animal laboratory of university-affiliated physiology institute.SUBJECTS Eighteen anesthetized merino sheep. INTERVENTIONS: A transit-time flow probe was placed around the left renal artery. Laser Doppler flow probes were inserted in the left renal medulla and cortex by micromanipulation to measure changes in regional intrarenal blood flow. MEASUREMENTS AND MAIN RESULTS: Systemic pressures, cardiac output, renal, and intrarenal blood flows were measured continuously. A bolus of Escherichia coli (7.5 x 10(9) colony forming units) was given intravenously to induce hyperdynamic sepsis. After the onset of hyperdynamic sepsis, all animals were randomly allocated to either norepinephrine (0.4 microg.kg-1.min-1 for 30 mins) or observation for 30 mins in random order. E. coli injection induced a significant decrease in mean arterial pressure (102.2 +/- 15.2 mm Hg to 74.3 +/- 16.1 mm Hg, p <.05) and an increase in mean cardiac output (4.60 +/- 1.62 L/min to 5.93 +/- 1.18 L/min, p <.05). However, renal blood flow did not change significantly (326.4 +/- 139.4 mL/min to 293.1 +/- 117.5 mL/min, not significant) despite a 30% increase in renal conductance (3.27 +/- 1.52 to 4.13 +/- 2.01 mL.min-1.mm Hg-1, p <.05). Cortical blood flow decreased by 15% (not significant) and medullary flow by 5% (not significant) during sepsis, but individual changes were unpredictable. On the other hand, norepinephrine infusion caused a significant improvement in mean arterial pressure (74.3 +/- 16.1 to 105.7 +/- 17.7 mm Hg, p <.05) and a further increase in cardiac output (5.93 +/- 1.18 to 7.13 +/- 1.52 L/min, p <.05). Mean renal blood flow also increased (293.1 +/- 117.5 to 384.5 +/- 168.1 mL/min, p <.05) despite decreased renal conductance (4.13 +/- 2.01 to 3.73 +/- 1.91 mL.min-1.mm Hg-1, p <.05). Infusion of norepinephrine significantly increased medullary blood flow by 35% compared with baseline (p <.05) and by 54% compared with untreated sepsis (p <.05), whereas the increases in cortical blood flow (16 and 53%, respectively) were not significant. CONCLUSIONS: Hyperdynamic sepsis caused renal vasodilation but had limited effects on regional intrarenal blood flow. Norepinephrine infusion (0.4 microg.kg-1.min-1) during sepsis significantly increased global and medullary renal blood flow and restored renal vascular tone toward but not above normal.     

Sequential physiologic interactions in pediatric cardiogenic and septic shock

We report that the pediatric cardiogenic shock and septic shock populations show similar hemodynamic and oxygen utilization physiologic relationships during aggressive intensive care therapy. We examined the mathematical relationships between vascular tone and flow, and oxygen utilization and oxygen delivery (DO2) in the early and middle stages of cardiogenic and septic shock. The fitted curves between cardiac index and systemic vascular resistance, and oxygen consumption (VO2) and DO2 were clinically and statistically similar in both shock populations. We found no evidence for decreased oxygen extraction in sepsis as compared to the cardiogenic shock population. In addition, it appears that the major determinant of VO2 in these populations is DO2, not oxygen extraction. We suggest that patients with cardiogenic or septic shock can be treated according to similar physiologic principles.     

The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock

Objective: To assess the effects of low-dose dopamine on splanchnic blood flow and splanchnic oxygen uptake in patients with septic shock. Design: Prospective, controlled trial. Setting: University hospital intensive care unit Patients: 11 patients with septic shock, diagnosed according the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference, who required treatment with norepinephrine. Measurements and main results: Systemic and splanchnic hemodynamics and oxygen transport were measured before and during addition of low-dose dopamine (3 μg/kg per min). Low-dose dopamine had a marked effect on total body hemodynamics and oxygen transport. The fractional splanchnic flow at baseline ranged from 0.15 to 0.57. In 7 patients with a fractional splanchnic flow less than 0.30, low-dose dopamine increased splanchnic flow and splanchnic oxygen delivery and oxygen consumption. In 4 patients with a fractional splanchnic flow above 0.30, low-dose dopamine did not appear to change splanchnic blood flow. Conclusion: Low-dose dopamine has a potential beneficial effect on splanchnic blood flow and oxygen consumption in patients with septic shock, provided the fractional splanchnic flow is not already high before treatment. Received: 19 September 1995 Accepted: 21 September 1996