Roger F. Higgins

Effects of Albumin Versus Non-albumin Resuscitation on Plasma Volume and Renal Excretory Function

Albumin, when added to a standard resuscitation regimen, is purported to enhance plasma volume, improve pulmonary function by its oncotic effect, and prevent renal failure by augmenting salt and water excreation. These factors were evaluated in a prospective randomized manner in 52 injured patients

Impaired Pulmonary Function after Albumin Resuscitation from Shock

The effects of albumin supplementation on pulmonary function were studied in 94 injured patients of whom 46 received albumin. The 94 patients received an average of 14.5 transfusions, 9.2 L crystalloid, and 0.9 L plasma in the emergency room and operating room; 46 patients received an average of 31 gm albumin during operation and 150 gm/day for 5 days. Blood pressure (BP), pulse, CVP, wedge pressure (PWP), red cell (RBCV), and plasma volumes (PV), total serum proteins (TSP), serum albumin (SA), cardiac output (CO), the per cent inspired oxygen/arterial O2 tension (FIO2/pO2), and the per cent of physiologic shunting in the lungs (p shunt) were noted serially following operation; only the first study on each patient was used for statistical correlations between the two groups. Albumin supplementation significantly (p =

The cardiac effect of altered calcium homeostasis after albumin resuscitation.

Supplemental albumin added to a standard non-albumin resuscitation regimen has been shown to significantly impair heartwork in seriously injured patients. The role of calcium dynamics in this myocardial depression was analyzed in 94 injured patients who were in shock for an average of 32 minutes, received an average of 14.5 transfusions, 9.2 L crystalloid, 0.9 L plasma, and 20.9 mEq calcium prior to the end of operation. By random selection, 44 patients received an average of 31 gms of albumin during operation, 207 gms during the early postoperative period (mean = 30 hrs) of extravascular fluid sequestration, and 402 gm during the mobilization period. The albumin resuscitated patients had normal total protein and serum albumin levels and higher total calcium (TC) levels, however, they had a significantly lower Ca++ and Ca++/TC. The accumulative slope for heartwork/filling pressure was significantly depressed in albumin patients as was the mean work unit/filling pressure index. The level of Ca++ and the Ca++/TC ratio correlated directly with the calculated work unit index in both the albumin and non-albumin patients. This suggests that a supplemental albumin binds serum Ca++ causing an increase in TC but a reduction in Ca++ and Ca++/TC. The fall in Ca++ and Ca++/TC seems responsible, in part, for heart failure and pulmonary edema in albumin resuscitated patients.

Differential Serum Protein Changes Following Supplemental Albumin Resuscitation for Hypovolemic Shock

The effects of supplemental albumin infusion on serum protein homeostasis were studied in 94 seriously injured patients who received an average of 14.4 transfusion, 9.2 L electrolyte solution, and 829 ml fresh frozen plasma before and during operation. Based on randomization, 46 patients received an average of 31 gm albumin during operation followed by 150 gm/day for 5 days; 48 patients received no albumin. Supplemental albumin caused a significant (p = less than 0.05) increase in total serum protein and albumin concentrations. In contrast, supplemental albumin caused a significant decrease in alpha 1 globulin, alpha 2 globulin, beta globulin, gamma globulin, and fibrinogen levels. The prothrombin time used as index of prothrombin concentration was significantly prolonged in albumin patients. These changes, not previously documented, need further evaluation to determine clinical significance.

Immunoglobulin Changes after Varied Resuscitation Regimens

Prior studies showed that albumin supplementation of the resuscitation for hypovolemic shock caused an increase in serum albumin but a fall in serum globulins; immunoglobulins were not measured. Using frozen sera, immunoglobulins (IgG, IgM, IgA, IgD) were measured in 184 severely injured patients including 40 patients prospectively randomized for supplemental steroid therapy and 46 patients prospectively randomized for supplemental albumin therapy. The remaining patients served as the control patients. Compared to normal, the control patients had a significant reduction in IgG, IgM, and IgA. This reduction was associated with a fall in total serum proteins and serum albumin concentrations. Supplemental albumin resulted in an increase in the serum albumin concentration but a reciprocal fall in the serum globulin fraction and in IgG, IgM, and IgA. The serum proteins and immunoglobulins in the steroid patients were significantly below normal but similar to that seen in the control patients. The reduction in serum proteins and immunoglobulins in the control and steroid patients paralleled the shock time (systolic pressure below 80 mm Hg) and the amount of plasma given during resuscitation. These correlations were not significant in the albumin- supplemented patients. These data indicate that albumin supplementation alters the normal immunoglobulin response to shock. These changes in the postinjury recovery period need further study.

Effects of Albumin on Serum Protein Homeostasis After Hypovolemic Shock

The effects of albumin on serum protein homeostasis were studied prospectively in 52 seriously injured patients who received an average of 15.3 transfusions, 9.7 liters of electrolyte solution, and 1 liter of fresh frozen plasma before and during operation. Based on randomization, 27 patients received an average of 25 g of albumin during operation followed by 150 g/day for 5 days, thereafter; 25 patients received no albumin. The cause of injury, volume needs during resuscitation, and severity of shock were similar for both groups. Sequential serum levels of total protein, albumin, α1-globulin, α2-globulin, β-globulin, γ-globulin, and fibrinogen and hourly disappearance of radioactive iodinated serum albumin (RISA) were measured for comparison. Patients given albumin had a significant (P < 0.05) increase in total protein and albumin levels throughout the first 6 days after operation. α1-Globulin levels were similar in both groups. In contrast, α2-globulin, β-globulin, γ-globulin, and fibrinogen levels were significantly decreased throughout the postoperative period in those patients receiving albumin. The hourly disappearance of labeled albumin was also increased in patients receiving albumin. These changes probably reflect a redistribution of albumin and globulin fractions in response to shock, although decreased production cannot be ruled out. Altered hemostasis and depressed immune response are two possible effects with clinical significance. Plasma volume and serum albumin concentration describe only the primary effect of albumin supplementation. Additional investigation of secondary homeostatic responses are necessary to more completely evaluate the effects of albumin infusion.

Negative Inotropic Effect of Albumin Resuscitation for Shock

The inotropic effects of albumin were studied in 94 seriously injured patients who received an average of 14.5 transfusions, 9.2 liters of crystalloid and 0.9 liters of plasma prior to end of operation; 46 patients, by random selection, received added albumin averaging 31 gm during operation, 198 gm during the early postoperative period of extravascular fluid sequestration, and 395 gm during the first 4 days of the later fluid mobilization period. Left ventricular stroke work index (LVSWI) was plotted against pulmonary wedge pressure (Ppw) in 22 patients who had indwelling thermistor pulmonary artery catheters at the time of the first study. Calculated heart work units (WU) were derived from the pulse pressure, mean arterial pressure, pulse rate, and central venous pressure (CVP) in patients without LVSWI measurements. Albumin supplementation increased serum albumin (4.2 vs. 2.9 gm%), plasma volume, CVP (15 vs. 9 cm H2O), but did not alter red cell volume (1,531 vs. 1,519 ml). The ratio of LVSWI/Ppw fell in albumin patients (1.9 +/- 1.6 vs. 4.8 +/- 1.8), and the ratio of WU/CVP was significantly depressed in albumin patients (4.9 +/- 2.3 vs. 7.3 +/- 2.1). The slopes of the LVSWI/Ppw and WU/CVP were shifted to the right in albumin patients. This negative inotropic effect was associated with impaired oxygenation, as reflected by an increased ratio of inspired oxygen per arterial oxygen tension (0.62 +/- 0.06 vs. 0.33 +/- 0.1). Finally, 24 of the 46 albumin-treated patients were digitalized for heart failure, compared to only 11 of the 48 nonalbumin patients. Pending subsequent studies, albumin should be considered a potentially negative inotropic agent.

Altered Coagulation after Albumin Supplements for Treatment of Oligemic Shock

Coagulation and need for postoperative blood and plasma therapy were studied in 94 injured patients requiring massive transfusions (average = 14.4); 46 patients, by random selection, received supplemental albumin. Albumin therapy increased total protein concentration (6.4 vs 5.8 g/dL), serum albumin level (4.2 vs 2.9 g/dL), and plasma volume (3,895 vs 3,579 mL) but not RBC volume (1,520 vs 1,530 mL). During the initial five postoperative days, patients receiving albumin required more transfusions (7.1 vs 3.8) and plasma (455 vs 317 mL). This increased need for blood and plasma correlated with a significant decrease in fibrinogen (238 vs 405 mg/dL) and prolongation of the prothrombin time (2.6 vs 1.4 seconds). The partial thromboplastin time was prolonged and the platelet concentration was decreased in albumin-treated patients, but not significantly. Deficiencies in specific coagulation factors have not yet been identified but are being studied. Impaired coagulation is another potential hazard of supplemental albumin therapy, which is probably contraindicated in injured patients.

Pulmonary Effects of Albumin Resuscitation for Severe Hypovolemic Shock

The effect of albumin when added to the resuscitation regimen of patients in hypovolemic shock was studied in a randomized prospective manner in 52 injured patients who received an average of 15.3 transfusions, 9.6 liters of balanced electrolyte solution, and 980 ml of fresh frozen plasma. Before and during operation, 27 patients received an average of 25 gm of albumin and 150 gm/day for three to five days. Patients who received albumin had greater dependence on respiratory support, averaging eight days while receiving ventilatory support with volume ventilator compared with three days in patients not receiving albumin. Furthermore, patients receiving albumin had forced inspiratory oxygen/Pao2 ratios that were statistically and significantly higher than those of patients not receiving albumin during all phases of their hospital course. These effects were associated with increased plasma volumes caused by the oncotic effects of albumin and by its interference with saline diuresis. On the basis of this preliminary report, albumin seems to have a detrimental effect on respiratory function.