Assessment of oxygenation in the critically ill

Transcription

1 Review Article Ann CIin Biochem 1991; 28: Assessment of oxygenation in the critically ill M C C Clapham From the Intensive Care Unit, East Birmingham Hospital, Bordesley Green Eust, Birmingham B9 SST, UK SUMMARY. This paper reviews the physiology and pathology of oxygen transport from the atmosphere to the cells in critically ill patients. A thorough understanding of this allows a rational approach to monitoring and managing an hypoxic patient in the intensive care setting. Additional key phrases: intensive care units; critical care; blood gas unalysis Oxygen is necessary for life. It is used to oxidize glucose, fat and amino acids to produce the energy needed for normal cellular function. Whcn the oxygen supply does not meet the demand, metabolism switches from the efficient aerobic to the less efficient anaerobic pathway. Interruption of the oxygen supply rapidly leads to Failure of cellular function because there is little stored oxygen in the body. The length of time a cell survives without oxygen varies in different organs: brain cells start to die after 3 min, whereas skin cells may survive much longer. Providing enough oxygen to prevent cellular damage and allow its repair is fundamental to managing critically ill patients. PHYSIOLOGY AND PATHOLOGY OF OXYGENATION Atmosphere to alveoli Oxygen reaches the tcrminal bronchiolcs by bulk gas flow and from there difuses into the alveoli.' All the alveolar oxygen is in the gaseous phase and thercfore its volume is directly proportional to its tension. The alveolar oxygen tension (PAO?) can be derived from equation (I).' PAO, = FiO: x (PB ~ PH20) - PACO,/RQ (1) The PAO, depends on the inspired oxygen fraction (FiO,), the barometric pressure (PB), the alveolar water vapour pressure (ph,"), the alveolar carbon dioxide tension (PACO,), and the respiratory quotient (RQ). The respiratory This paper was prepared at the invivation of the Clinical Laboratory lnves~iyation Sub-cuinini~~ee of thc Scientific Cominillee of llic Association ofclinical Riochcmiaia, but does no1 necessarily relleci 'heir views. quotient is included becausc volume for volume the body's consumption of oxygen is greater than its production of carbon dioxide (normally 250 and 200 ml/min, respectively). The PACO, is not usually measured and for calculation purposes it is assumed to be the same as the arterial carbon dioxide tension (PaCO,). The barometric pressure is determined by altitude and meteorological factors, while the water vapour pressure is 6.3 kpa at 37 C. Effect of changes in FiO, and PACOz The FiO, of air is about 0.21 which can be increased to a maximum of 1.0 by adding oxygen to the inspired gases. In the presence of normal PACOz (5.3 kpa), PB (101 kpa), P,,20 (6.3 kpa), and RQ (0.8) the PAOz will rise from 13.3 to 88.1 kpa when the FiO? is increased from 0.21 to 1.0 (equations 2 and 3). (FiO, = 0.21, PACO, = 5.3) PAO, = 0.21 x ( ) - 5.3/0'8 = 13.3 (2) (FiO, = 1.0, PACOz = 5.3) PA02 = 1.0 x ( ) - 5.3j0.8 = 88.1 (3) The carbon dioxide level in the alveoli is determined by the balance between that produced from metabolism and that removed by ventilation (equation 4). An increase in production will raise the PACO, while an increase in removal will lower the PACO?. CO, production alveolar CO, = (4) alveolar ventilation 27

2 28 Clapham The PACO, has a clinically significant effect on the PAO, only with a normal FiO, of This is illustrated below where the PACOz is increased from the normal 5.3 kpa to 10 kpa with an FiOz of 0.21 and 1.0 (equations 5 and 6). (FiO, = 0.21, PACO, = 10) PAO, = 0.21 x ( ) - 10/0.8 = 7.4 (5) (FiO, = 1.0, PACO, = 10) PA02 = 1.0 x ( ) - loj0.8 = 82.3 (6) The doubling of PACO, almost halves the PAOz at an Fi0, of 0.21, yet produces no clinically significant effect at an FiO, of 1.0. Alveoli to blood Oxygen diffuses down a pressure gradient from the alveolar space through the alveolar-capillary membrane and dissolves in the plasma. At a normal arterial oxygen tension of I3 kpa, a litre of plasma contains about 3 ml of oxygen. Were it not for the presence of haemoglobin, 83 L/min of plasma would be needed to meet the body s normal oxygen requirement of 250 ml/min. Oxygen diffuses from the plasma into the red blood cells to combine with haemoglobin (Hb) to form oxyhaemoglobin (HbO,). The movement of oxygen from the plasma causes the tension to fall and more oxygen diffuses from the alveoli into the plasma. This continues until an equilibrium is reached or the blood flows on. The saturation (SO,) is the percentage of the Hb present as HbO,. Each gram of Hb can carry a theoretical maximum of 1.39mL of oxygen (the Hufner factor). The volume of oxygen carried in the blood, the content (C), is the sum of that combined with Hb and that dissolved in the plasma (equation 7). oxygen content (ml/l) = (7).., (Hb x SO, x 1.39) (PO, x 0.23) where PO, = dissolved oxygen tension (kpa) 0.23 = volume of dissolved oxygen (ml/l) for each kpa PO, Hb = haemoglobin concentration Intra-pulmonary shunts If all the alveoli were perfectly ventilated and perfectly perfused, the arterial blood would have the same composition as the blood leaving the alveoli (end-capillary blood). However, some blood perfuscs the lungs without coming into contact with alveolar gas (shunt) whilst some ventilated alveoli are not perfused (dead space). The shunted blood mixes with the end-capillary blood to become arterial blood. In normal people there is a small shunt due to mismatching of ventilation and perfusion. This increases in critically ill patients, particularly those with respiratory problems. Inadequate Ventilation of alveoli may be due to their collapse or to their being filled with fluid. The increased shunt causes a fall in arterial oxygen content and PaOz. The effect of shunting on arterial oxygen content is shown in equation (8). CaO, = cco, x (I-sf) + CVO, x sf (8) CaOz = arterial oxygen content CcO, = end-capillary oxygen content CvO, = mixed venous oxygen content sf = fraction of the flow bypassing the alveoli With no shunt (sf = 0) the arterial blood has the same oxygen content as the end-capillary blood and the PaO, will equal the PAOz. As the shunt increases, with no changc in CcO, or CvOz, the CaO, will fall and the PaO, will be lower than the PAO,. Because of the sigmoid relationship of PO, to blood oxygen content, the fall in PaOz is not linear with respect to the increase in shunt. As most of the oxygen is carried as HbOz the smaller dissolved fraction can be ignored for the purposes of the following explanation. In equation (8) Ca, Cc and Cv each relate to the same Hb concentration and Hufner factor and their elimination gives equation (9). SaO, = ScO, x (I-sT) + SvO, x sf (9) SaOz = arterial saturation ScO, = end-capillary saturation SvO, = mixed venous saturation With no shunt (sf = 0) the SaO, equals the ScO,, which with an FiO, of 0.21 would be about 96%. With a 50% shunt (sf = 0.5), SvO, 75%, and FiO, 0.21 the SaO, would be about 85.5%. Increasing the FiO, to 0.5 would raise the ScOz to 100% and, with the SvO, staying at 75%, the SaO, would rise to 87.5%. Inspection of the oxygen dissociation curve (Fig. I) shows this is only a small increase in PaO,. This shows why a low PaO, that is due to a large shunt cannot be successfully treated by increasing FiO, alone (Table I).

3 Assessment of oxygenation in the critically ill 29 CvOz = mixed venous content (ml/l) C.O. = cardiac output (L/min) i I0 MEASUREMENT OF OXYGEN CONTENT AND DELIVERY AND CONSUMPTION Before the blood oxygen content is measured, the quality of the sample must be considered. Has the sample been properly collected, stored and transported? If the sample is not representative then however good the quality of the analysis, the information will be useless.' TABLE I. Effi.c.1 of'fio, 0/0.21 und 0.5 on ihr urlrriul PO, wiih shunts of 10% und 50% End-capillary Arterial F102 P02(kPa) Sat(%) PO,(kPa) Sat(%) ~ 50"h shunt with mixed venous saturation of 75%: % shunt with mixed venous saturation of 75%: Total oxygen delivery The cardiovascular system transports oxygenated blood from the lungs to the tissues and returns deoxygenated blood to the lungs. The total oxygen delivery is the product of the arterial blood oxygen content and the cardiac output (equation 10). DO, = CaOz x C.O. (10) DOz = oxygen delivery (ml/min) CaOz = arterial oxygen content (ml/l) C.O. = cardiac output (Ljmin) Total oxygen consumption The oxygen consumption is the difference between the oxygen delivered to the tissues and the oxygen returned to the pulmonary artery as mixed venous blood (equation 11). VO, = (CaO, x C.O.) - (CvO? x C.O.) = (CaO, - CvO,) x C.O. (1 1) VO, = oxygen consumption (ml/min) CaO, = arterial oxygen content (ml/l) Direct measurement of oxygen content Van Slyke4 described a direct method for measuring oxygen content in The principle of this method is to liberate all the oxygen from the blood sample and measure its volume. However, it is a time consuming technique that requires experienced laboratory staff to produce reliable and accurate results. It is a technique that does not lend itself to automation and is now usually reserved for research as it is still the 'gold standard'. Other methods of direct measurement have been described but have not gained widespread a~ceptance.~ Derived oxygen content In clinical practice oxygen content is derived from equation (7) after measurement of the individual components. Accurate measurements of Hb and the PO, are readily available in most hospitals, but not SOz. Historically POz measurement using the Clarke electrode6 was introduced before the methods for measuring Hb saturation, thus PO, has become the usual method for the objective assessment of blood oxygenation. Haemoglobin saturation can be reported in two ways, either as a percentage of the total Hb or as a percentage of Hb available for oxygen transport, i.e. the sum of oxygenated and reduced Hb. If all the Hb was available to carry oxygen, theoretically each gram could accomodate 1.39 ml of oxygen. However, when Hufner measured the oxygen carried by Hb he found that each gram carried 1.34mL of oxygen.' This figure probably reflected all the Hb moieties, including small proportions of Hb that cannot carry oxygen such as carboxyhaemoglobin and methaemoglobin. This may explain why the derived Hufner factor can vary between 1.34 and There are now two sorts of oximeters in general use, co-oximeters which measure saturation on blood samples drawn from patients and

4 30 Clapharn pulse oximeters which measure saturation noninvasively in intact patients. Modern cooximeters measure the SO, and Hb accurately and rapidly but are not yet widely available. The alternative is to calculate the SOz from the PO, and the oxygen dissociation curve (ODC). The ODC is sigmoid because each Hb molecule can combine with four oxygen molecules and the ease with which each attaches varies (Fig. I). The calculated SO, is unreliable because the shape and the position of the ODC can be changed by physiological and pathological conditions. An increase in carbon dioxide. hydrogen ion concentration, temperature or 2,3-diphosphoglycerate (2,3-DPG) concentration will shift the curve to the right. Conversely, a decrease in any of these will move the curve to the left. In normal individuals the calculated SO2 was found to be unacceptable for deriving oxygen contents in normal adultsx Critically ill patients frequently have derangements which will displace the ODC and errors in the calculated SOz are more likely. Therefore deriving oxygen content from a calculated SO, cannot be recommended. Oxygen delivery The oxygen delivery is the product of the cardiac output and the arterial oxygen content. Cardiac output can be measured invasively utilizing the Fick principle, by dye dilution or thcrmodilution. The Fick principle states that the amount of substance taken up by an organ per unit time is equal to the arterial level of the substance minus the venous level times the blood flow (see equation 11). Cardiac output can be measured non-invasively by doppler ultrasound or thoracic cavity impedance. At present the accepted standard technique is the thermodilution method. This requires the insertion of a catheter into the pulmonary artery and can only be safely offered in units specializing in the technique. HOW MUCH OXYGEN IS ENOUGH? The simple answer is that enough oxygen is being supplied whcn each cell gcts cnough oxygcn to meet thc demand. The difficulty is to identify when this occurs or when it does not. Since it is not possible to monitor each cell individually or even each organ, cruder methods such as total body oxygen requirements have to be used. Since the introduction of the Clarke electrode, conventional belief has held that an arterial PO2 > 9.3 kpa is adequate. This value is associated with a near maximal saturation of Hb. and thus oxygen content assuming a normal ODC. As the ODC moves to the right a higher PO, is required to maintain the same saturation. The usual method of describing the ODC s lucation is the P50, i.e. the tension at which Hb is 50% saturated. As many clinicians find the P50 difficult to interpret the P95, the POz at 95% saturation, may be a suitable alternative. When the ODC is right shifted the P95 will increase. A single measurement of POz and SOz can be used to calculate the position. At first glance a right shifted ODC suggests a decrease in oxygen availability to the tissues because the arterial content falls for a given POz. However the availability at the cellular level increases because more oxygen is liberated for a given capillary PO,. The mitochondria need a PO, of kpa to function. Therefore the capillary PO2 needs to be at least 2-7 kpa to provide an adequate pressure for the oxygcn to diffuse to the mitochondria. Calculation of the volume of oxygen released when the PO, falls from an arterial level of 10 kpa to 2.7 kpa reveals that more oxygen is released when the ODC is the shifted to the right (Table 2). Calculation of this theoretical conditional extraction is one mcthod of integrating the PO,, the Hb, the SO2 and position of the ODC to a single parameter. Contents ml/l PO, SO2 Hb (yo) (gidl) Arterial Ven (2.7 kpa)* Arterio-venous difference Normal Right Ven (2.7 kpa) is the venous content assuming a PvO, of 2.7 kpa.

5 Assessment of oxygenution in the critically ill 31 The detection of arterial hypoxia has been made easier by the introduction of affordable non-invasive pulse oximetry. The pulse oximeter works on the same principles as whole blood oximetry but shines the light through a finger or an ear lobe. It is able to separate the background signals from those of the arterial pulse and thus measure arterial saturation. Pulse oximetry is not as accurate as blood gas analysis, and it does not provide the additional variables, such as carbon dioxide tension and acid base balance, that are available from blood gas analysis. Therefore pulse oximetry should be used in conjunction with blood gas analysis rather than as an alternative. Lactate When the oxygen delivery does not meet the demand, metabolism changes from aerobic to anaerobic. Pyruvate is converted into lactate rather than into carbon dioxide and water via Krebs cycle. A rise in blood lactate concentration is thus indirect evidence of inadequate oxygen delivery. In a group of shocked patients a blood lactate > 57mmol/L was associated with I00% m0rta1ity.l~ Unfortunately a rising blood lactate is a late feature of tissue hypoxia, by which time irreparable cellular damage may have occurred. Lactate measurement thus tells the clinician what has already occurred rather than warning of impending problems. Delivery dependent oxygen consumption Oxygen delivery normally exceeds oxygen demand, thus as delivery decreases demand is still met, and oxygen consumption is indepcndent of oxygen delivery at high levels of delivery. However, if oxygen delivery falls below a certain point oxygen consumption becomes delivery dependent and decreases in proportion to the fall in delivery. Conversely, if the oxygen consumption does not increase in response to a rise in delivery, the implication is that the oxygen demand has been satisfied. Although this is theoretically attractive as a method of detecting inadequate oxygen delivery, it has not been proven to be of benefit in clinical use. Clinical outcome Shoemaker and colleagues made serial measurements of a large number of physiological parameters in critically ill post-operative patients. The variables were ranked according to their association with survival. The four most important variables associated with survival were blood volume, cardiac output, oxygen delivery and oxygen consumption. These are all related to perfusion of tissues. These four variables were all required in amounts greater than the normal physiological values. indicating that not only do supranormal amounts of oxygen need to be delivered but supranormal amounts needed to be utilized. A prospective trial then compared a control group, managed conventionally, with a treatment group managed by adjusting physiological parameters to those values associated with survival (Table 3). The patients were randomly allocated and of equivalent degrees of illness. The treatment group had a mortality of 13% and the control group 48%. This difference is both statistically and clinically significant. The oxygen consumption of a group of high risk surgical patients has been followed perioperatively. * The oxygen debt was calculated as the difference between the measured oxygen consumption and the estimated oxygen requirements. Survivors with organ failure incurred a lower oxygen debt (26.8L) than the non-survivors (33.5 L). Furthermore, the survivors without organ failure had a lower oxygen debt (8.0 L) than the survivors with organ failure. These studies support the premise that cellular and organ failure follow inadequate oxygen delivery and utilization. Furthermore, they suggest that adjusting patients physiological parameters into the range associated with survival can improve outcome. At present the methods for deriving the data for oxygen delivery and consumption require the use of complex invasive monitoring. Therefore it is necessary to have a rational approach to the TABLE 3. Guidelines for therupy ofcriticul1.v ill surgical purients in order OJ lemporul priority Blood volume > 2.7 L/M2 for women > 3.0 L/M2 for men Cardiac index > 4.5 L/M2 0, delivery > 550 ml/min.mz 0, consumption > 167 ml/min.mz Blood pressure normal Wedge pressure c 20mmHg Pulmonary vascular resistance < 250 dyne.cm/ss.m2 PaO, > 9.3 kpa SaO, > 90% ph > 7.3 and i 7.5 PvO, z 4.0 kpa

6 32 Cluphum Atmosphere Alveoli PAO, = FiO, x (PB- P 1- PACO, / RQ H20 End capillary / \ CvO, = Ca02- VO, u Mixed venous - Arterial Delivery = arterial content x C.O. C.O. =(HbxS02x1.39t PO2x0.23) xc Con su m pt ion = (COO,-CvO, 1 x C.0 FIGURE 2. Overview qfo.~.ygm transporffrom the u/mosphere to /he lissues. Symbols urc (IS tlt.finc~l rn rez/ iequtrrions 1,7.10,11/. C.O. = cardiac output monitoring and management of hypoxic patients. MANAGEMENT OF HYPOXIA Hypoxia can be rationally managed by considering Fig. 2 and equation (8). The arterial oxygen content, and thus the PaOz. depends on the end-capillary content, the mixed venous oxygen content and the degree of sbunt. As shown earlier, the end-capillary oxygen content depends on the alveolar PO2 and the Hb concentration. Therefore adjustment of the FiO, by adding oxygen, the PACO, by ensuring adequate ventilation, and Hb by transfusion will optimize the end capillary content. The shunt fraction can be decreased by improving ventilation of partially and totally collapsed alveoli. These can be re-inflated by applying positive pressure to the airway either as intermittent positive pressure ventilation (IPPV) with positive end expiratory pressure (PEEP) or by continuous positive airway pressure (CPAP). Unfortunately, the application of PEEP/CPAP can decredse the cardiac output, by increasing the intra-thoracic pressure and decreasing the return of blood to the heart. A fall in cardiac output will decrease the total oxygen delivery. Therefore an increase in arterial oxygen content achieved with PEEP/CPAP has to balanced against a potential fall in cardiac output, the aim being to increase the overall oxygen delivery. The mixed venous oxygen content is determined by the oxygen delivery and oxygen consumption as shown by rearrangement of equation (1 l). vo, = C.O. x (CaO, - CVO,) The mixed venous content can be increased by: I. increasing the cardiac output 2. decreasing the oxygen consumption 3. increasing the arterial oxygen content. Thc information required for the managcment of hypoxia is summarized in Table 4. Oxygen toxicity Excess oxygen can cause convulsions, pulmonary damage and retrolental fibroplasia. Convulsions occur when the oxygen tension is greater than 2 atmospheres. The mechanism is unclear but is associated with a decrease in gammaaminobutyric acid in the brdin. Pulmonary damage includes a decrease in type I and increase in type 2 alveolar cells, absorption collapse of TAHLE 4. Vuriuhles rryuired fir munurement of hypoxiu in the criticully ill ~ ~~ Measured values PaCO, Hb Pa02 SaO, Cardiac output svo, PVOZ Derived values Alveolar 0, End capillary content Arterial content: (ODC position) (Conditional extraction) Oxygen delivery Mixed venous content Oxygen consumption

7 A.s.se.ssrn~~nt of oxygenution in the critically ill 33 alveoli, and ventilatory depression. The type I cells line the alveoli and are derived from type 2 cells, which do not act as gas exchange membranes. It appears that it is the oxygen tension rather than its concentration that determines pulmonary toxicity. The use of 100% oxygen at I atmosphere for short periods seems to be safe. On our ITU the use of more than 60% oxygen for more than 4 h is avoided if possible. SUMMARY AND RECOMMENDATIONS The provision of adequate oxygen to the cells is the primary aim of thc management of the critically ill in the ITU. Achieving this requires a rational approach to therapy which itself requires a thorough understanding of how oxygen normally rcaches the cells (Fig. 2) and effective monitoring of this process. The equipment required includes a blood gas analyser and co-oximetcr. The precise method of presenting the data has not be standarized or agreed upon. In presenting the data it is important to distinguish between measured and derived values because even a small error in measurement or its documentation may be magnified in the derived values. This may then result in inappropriate interpretation and management of the patient. A comprchensivc understanding of the physiology and pathology of oxygenation remains the single most important factor in managing the critically ill. REFERENCES I West JB. Respirutory Physiology -~ the Esscmriuls. Baltimore: Williams and Wilkins Company, 1974; 6 2 West JB. Rrspirulory Physiology - /he E.ssentiu1.s Baltimore: Williams and Wilkins Company, 1974; 54 3 Biswas CK, Ramos JM, Agroyannis BA, Kerr DNS. Blood gas analysis: effect of air bubbles in syringe and delay in estimation. Br Med J 1982; 284: Van Slyke DD, Neil JM. The determination of gases in blood and other solutions by vacuum extraction and manometric measure. I J Bid Chem 1924; 61: Zander R, Lang W, Wolf HU. Oxygen cuvette: a simple approach to the oxygen content measurement in blood. Pflugers Arch 1977; 368: R16 6 Clark LC. Monitoring and control of blood and tissue O2 tensions. Truns Am Soc Artf0rgan.s 1956; 2: 41 7 Astrup P. Severinghaus JW. The History uf Bkood Gusc,s, Acids and Buses. Copenhagen: Munksgaard International Publishers, 1986; 122 X Willis N, Clapham M. The validity of oxygen content calculations. Clin Chim Acru 1985; 150: Levett JM, Replogle RL. Thermodilution cardiac output: A critical analysis and review of the literature. J Surg Res 1979; 27: I) Tremper KK. Continuous noninvasive cardiac output: Are we getting there? Crit Cure Med 1987; 15: I Shoemaker WC, Appel P, Bland R. Use of physiological monitoring to predict outcome and to assist in clinical decisions in critically ill postoperative patients. Am J Surg 1983; 146: Willis N. Clapham MCC, Mapleson WW. Additional blood gas variables for the rational control of oxygen therapy. Br J Anues 1987; 59: Bryan-Brown CW, Baek S, Makabali G. Shoemaker WC. Consumable oxygen: availability of oxygen in relation to oxyhemoglobin dissociation. C rit Cure Mcd 1973; 1: I Hardway RM. Prediction of survival or death of patients in a state of severe shock. Surg Gynecol Ohst( / 1981; 152: Schumaker PT. Cain SM. The concept of a critical oxygen delivery. Intensive Cure Mid 1987; 13: Bland R. Shoemaker WC, Shabot MM. Physiologic monitoring goals for the critically ill patient. Siq G,vti(,(.OI Oh.vt( / 1978; 147: Shoemaker W, Appel PL, Waxman K. Schwartz S. Chang PC. Clinical trial of survivors cardiorespiratory patterns as therapeutic goals in critically ill postoperative patients. Crit Cure Med 1982; 10: Shoemaker WC, Appel PL, Kram HB. Tissue oxygen debt as a determinate of lethal and nonlethal postoperative organ failure. Crit Cure M d 1988; 16: I J F Nunn. Applied Respirutorj Physiology, 3rd ed. Sevenoaks: Butterworths. 1987; Accepted for publication 3 August 1990