Robert Schlichtig

Tissue-arterial PC02 difference is a better marker of ischemia than intramural pH (pHi) or arterial pH-pHi difference

Gastric intramucosal pH (pHi) is often calculated by the Henderson-Hasselbalch equation, using arterial plasma [HCO3-]ap and PCO2 measured in saline obtained from a silastic balloon tonometer after equilibration in the lumen of the stomach. A pHi value less than approximately 7.3 pH units is often taken as evidence of intestinal ischemia. An alternative measure is tissue PCO2 (PtCO2)-PaCO2 difference [P(t-a)CO2]. The idea is that PtCO2 will increase slightly relative to PaCO2 as O2 supply decreases, and then increase strikingly when flow decreases to a critical value, because of liberation of CO2 from tissue Hco3- by anaerobically generated strong acid. A third method is arterial plasma pH (pHap)-pHi difference [pH(ap-i)]. We used mathematical simulations to test the hypotheses that calculated pHi is independent of arterial acid-base status; and pH(ap-i) provides the same information as does P(t-a) CO2. Using the Van Slyke version of the arterial whole blood [standard base excess] ([SBE]aWB) equation, it was found that a change in [SBE]aWB at constant PaCO2 and constant PtCO2 produces a change in calculated pHi (P = 0), such that the relation between changing [SBE]aWB and changing pHi is predictable by a single polyomial equation (R2 = .999). pH(ap-i) avoids this confounding influence of [SBE]aWB. However, it was further shown that pH(ap-i) can be associated with a wide range of P(t-a)CO2, depending on the magnitude of pH(ap-i), and on the PaCO2 at which P(t-a)CO2 is measured. We conclude that P(t-a)CO2 is a more reliable index of gastric oxygenation than is pHi alone or pH(ap-i).

Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms.

Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no-flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical-triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free-radical reactions, DNA cleavage, and transient extracerebral organ malfunction? For future mechanism-oriented studies of the brain after cardiac arrest and innovative cardiopulmonary-cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points.

Arteriovenous pH and Partial Pressure of Carbon Dioxide Detect Critical Oxygen Delivery During Progressive Hemorrhage in Dogs

Arteriovenous (AV) pH and PCO2 gradients increase as flow decreases and might potentially detect “dysoxia,” ie, inadequate tissue O2 delivery (DO2). However, expanding AV pH and PCO2 gradients previously have been attributed to respiratory acidosis lie, pH that decreases only in proportion to increasing CO2, an expected consequence of flow that is decreased but not necessarily inadequate). We studied AV pH and Pco2 during O2 supply independence, wherein O2 consumption (VO2) does not vary with DO2, and O2 supply dependence, a pathologic condition wherein VO2 and DO2 co-vary, in 14 dogs during graded progressive hemorrhage. Critical DO2 (DO2c), estimated by dual line regression, was 7.04 ± 0.30 mL/ kg min (SE). Arteriovenous pH and AV Pco2 also varied with 1502 in a biphasic fashion, with inflections occurring at very similar DO2 values (8.71 and 6.84 mL/kg min, respectively). Arteriovenous pH increased in proportion to expanding AV PCO2 during O2 supply independence, consistent with a “respiratory” etiology of AV pH in this region. During O2 supply dependence, however, the response of AV pH to AV Pco2 was greater, such that the linear regression of O2 supply dependent AV pH versus AV Pco2 was significantly different from the O2 supply independent regression (P < .001). Our data support the hypothesis that rapidly expanding AV pH and AV Pco2 represent metabolic acidosis and that these parameters may potentially be used to detect dysoxia.

[Base Excess] vs [Strong ION Difference]

Blood [base excess] ([BE]) is defined as the change in [strong acid] or [strong base] needed to restore pH to normal at normal PCO2. Some believe that [BE] is unhelpful because [BE] may be elevated with a “normal” [strong ion difference] ([SID]), where a strong ion is one that is always dissociated in physiological solution, and where [SID] = [strong cations] — [strong anions]. Using a computer simulation, the hypothesis was tested that [SID] = [SID Excess] ([SIDEx]), where [SIDEx] is the change in [SID] needed to restore pH to normal at normal PCO2. The most current version of the plasma [SID] ([SID]p) equation was used as a template, and an [SIDEx] formula, of the Siggaard-Andersen form, derived: \({\left[ {{\text{SIDEx}}} \right]_p} = {\left[ {HC{O_3}^ - } \right]_P} - 24.72 + \left( {p{H_p} - 7.4} \right) \times \left( {1.159 \times {{\left[ {{\text{alb}}} \right]}_p} \times + 0.423 \times {{\left[ {Pi} \right]}_p}} \right)\). [SID] was compared to [SIDEx] over the physiologic range of plasma buffering, and it was found that [SIDEx] varied by ~ 15 mM at any given [SID], thereby faulting the hypothesis. It is concluded that [SID] can be “normal” with an elevated [SIDEx], the latter being an expression of the [BE] concept, and a more helpful quantity in physiology.

CURRENT STATUS OF ACID-BASE QUANTITATION IN PHYSIOLOGY AND MEDICINE

Acid-base balance (ABB) is best determined by measurements in arterial whole blood, but for clinical purposes it can be expressed as estimated to apply to the entire extracellular fluid (ECF) of the body. ABB is determined by three independent variables: (1) respiratory (P co2); (2) metabolic (strong ion difference [SID]); (3) nonvolatile weak acid buffer (ATOT), primarily hemoglobin (Hb). Here we describe and compare four current indices of the metabolic component: (1) Standard base excess (SBE), in mM⋅L–1, quantifies the metabolic component, by assuming that the mean buffer strength of the ECF in humans equals that of blood with 5 g/dL hemoglobin. Despite individual variation of hemoglobin, the effective ATOT of ECF in vivo is practically invariant. SBE is automatically computed by most blood gas analyzers from P co2 and pH. (2) SID between plasma strong cations and anions, numerically equal to buffer base, as modified to apply to ECF in vivo. (3) HCO3– calculated from pH and P co2. Because pH and HCO3– vary with both P co2 and SID, equations are needed when this method is used to compare the sample with the usual or expected compensation for an ABB abnormality. Such computations do not produce a measure of the metabolic component. (4) Anion gap, Na+ + K+ − Cl– − HCO3–, detects anions not normally measured by plasma electrolyte screens. It can distinguish acidosis due to excess Cl– from that of other strong anions such as lactate. Using published pH (or H+) and HCO3– data, we have computed the typical compensatory responses of patients with primary acid-base imbalances in terms of SBE and Pa co2:

Adult respiratory distress syndrome associated with epidural fentanyl infusion.

Objective: To determine the cause of unexplained postoperative adult respiratory distress syndrome (ARDS). Design: Case‐control study of postoperative ARDS. Setting: Intensive care unit (ICU) of a Veterans Affairs hospital. Patients: Six postoperative patients recovering from uncomplicated vascular or cardiothoracic surgery developed unexplained ARDS. Controls were 17 patients having similar procedures without the development of ARDS. Intervention: Infusion of fentanyl with a tamper‐proof device. Measurements and Main Results: Development of ARDS. ARDS began 1 to 4 days after surgery, was characterized by maximum alveolar‐arterial oxygen gradient that ranged from 232 to 544 torr (30.9 to 72.5 kPa), and was associated with death of two patients. We observed no association with patient location before ARDS onset, nonanalgesic medication administered, staff assignment, or mode of respiratory therapy. All six patients who developed unexplained ARDS had received epidural fentanyl compared with none of 17 control patients without ARDS ( p = .0002). We instituted a tamper‐proof mode of parenteral fentanyl administration, and subsequently observed one case of ARDS in 26 consecutive surgical patients ( p = .000014). Conclusions: Based on these findings, as well as a prior history of fentanyl theft at our institution, we conclude that tampering with fentanyl infusate was responsible for the ARDS epidemic that we observed. (Crit Care Med 1994; 22:1579–1583)

Regional oxygen delivery in oxygen supply-dependent states

Assessment of the adequacy of systemic O2 delivery (DO2) is central in the evaluation of critically ill patients, but estimates of systemic DO2 do not assess the effectiveness of regional DO2 to all vascular beds whose functions may require different degrees of blood flow depending on their metabolic and functional demands. The oxygen supply-consumption curve includes a supply-in-dependent portion, which represents the reserve capacity of the body to maintain oxygen consumption (VO2) despite inadequate increases in DO2, and a supply-dependent portion, which represents the physiologic adaptation that occurs once DO2 is unable to meet the metabolic demands of the body. Experiments in dogs revealed that when systemic DO2 was progressively reduced, blood flow was maintained in the vital organs (heart and brain) and redistributed away from the kidneys and liver, enhancing the ability of the whole organism to use oxygen efficiently. Disease states and iatrogenic conditions that alter this vasoregulatory process may directly impair organ system function.

Critical O2 delivery in rat brain.

As O2 delivery (DO2) of whole body,1,2 intestine,3,4 liver,5 or skeletal muscle6 is progressively decreased in anesthetized animals, O2 consumption (VO2) is initially maintained constant via increased O2 extraction by the tissues (O2 supply independence). However, below a critical threshold DO2 value (DO2c), VO2 of these organs decreases in proportion to DO2 (O2 supply dependence). More importantly, dysoxia (i.e. O2 demand that exceeds O2 supply)7 appears to commence at the onset of liver O2 supply dependence, as reflected by the simultaneous decrease in VO2 and increase in hepatic mitochondrial reduction.5 Accordingly, it tentatively appears that dysoxia may be identified, in liver at least, by the DO2c inflection of a biphasic VO2- DO2 relation.