Dennie Grabow

Fresh frozen plasma supplement to massive red blood cell transfusion.

The efficacy of supplemental fresh frozen plasma (FFP) therapy after massive packed red cell (PRBC) replacement for hemorrhagic shock was studied in 22 conditioned dogs. Ten dogs were randomized to received FFP, balanced electrolyte solution (BES), and PRBC, while 12 dogs received BES and PRBC. Coagulation factor activity for Factors I, II, V, VII and VIII, as well as antithrombin III (AT III), prothrombin time, partial thromboplastin time, and thrombin time, were measured at preshock, postshock, postresuscitation, and postshock day two. All coagulation factor activities fell with shock and decreased further with resuscitation in both groups. Factor II (a procoagulant) and AT III (an anticoagulant) fell significantly less after resuscitation in the plasma dogs; otherwise, no postresuscitation differences were seen. The changes in factor activity from postresuscitation until day two reflected factor half life and molecular weight, independent of FFP therapy. These data show that prophylactic FFP therapy does not efficiently restore coagulation activity. Consequently, routine FFP therapy for its procoagulant effects after hemorrhagic shock should be abandoned pending controlled studies in man.

Colloid Oncotic Pressure and Body Water Dynamics in Septic and Injured Patients

Colloid oncotic pressure (COP) and fluid shifts were studied in 43 septic (SS) patients and 33 injured (HS) patients (ISS = 48.2). During maximal postresuscitation fluid retention, plasma volume (PV/RISA), red cell volume (RBC/51Cr), inulin space (ECF), and COP were measured. Interstitial space (IFS), PV/IFS ratio, and correlation coefficients (r) were calculated. A subgroup of 22 SS patients and 22 HS patients of equal study weight were also compared. Septic patients had greater IFS expansion (17.6 L vs. 11.5 L) than HS patients who, by inference, had more intracellular expansion. Expansion of IFS in SS patients correlated (r = -0.76, p less than 0.02) with reduced plasma COP; this was not seen in HS patients (r = -0.09, p less than 0.35). In contrast, plasma COP correlated (r = 0.72, p less than 0.001) with PV/RISA in HS patients but not in SS patients (r = 0.09, p greater than 0.35). We conclude: (1) SS patients with greater IFS expansion that correlates with reduced plasma COP likely have increased capillary permeability; and (2) HS patients with less IFS expansion that does not correlate with reduced plasma COP likely have maintained capillary permeability with altered IFS matrix configuration causing reduced protein exclusion.

The effects of Hespan on serum and lymphatic albumin, globulin, and coagulant protein.

The effects of hydroxycthyl starch (Hespan) resuscitation on serum and lymphatic proteins following hemorrhagic shock were studied in 34 splcnectomizcd dogs. Following shock, five randomly assigned treatment groups received the shed blood plus 50 mL/kg of salt solution (RL) or RL with varying concentrations (0.22–1.5 gm/kg) of Hespan. Each dog received 50 ml/kg/d of the test solution for three days after shock. Prothrombin time, partial thromboplastin time, thrombin time, total serum protein, albumin, globulin, and coagulant protein activity of fibrinogen, prothrombin, and factor VIII were measured before shock, at the end of shock, following resuscitation, and on day 3; thoracic duct lymph values were obtained on day 3. Hespan-supplemented resuscitation lowered all serum proteins including albumin, globulin and coagulant proteins; concomitantly, the lymph protein rose after Hespan resuscitation. This decrease in scrum proteins and rise in lymph proteins parallels similar results after albumin resuscitation in man and animals and suggests that Hespan induces an oncotically controlled extravascular protein relocation. Further studies on the significance of these findings need to be conducted.

Efficacy of liver wound healing by secondary intent

Nonoperative treatment of liver injury raises questions about liver wound healing (LWH) when the edges are not approximated by primary intent. The efficacy of LWH was studied in 18 dogs and 18 pigs with a total of 108 standard 6-cm injuries. The 36 injuries in six dogs and six pigs were compressed for hemostasis and then allowed to heal by second intent. LWH in these animals was compared to 36 liver wounds in six dogs and six pigs following primary closure (hepatorrhaphy) and 36 liver wounds after omental buttress plus hepatorrhaphy in six dogs and six pigs. Average wound breaking strength (WBS) of liver wounds was studied at 3 weeks (54 wounds) and 6 weeks (54 wounds) with a Chatillon tensiometer and microscopic analysis. The WBS of liver wounds was also compared to normal uninjured liver WBS. The porcine WBS at 3 weeks after healing by second intent (0.31 kg/cm2) was similar to the WBS at 3 weeks after healing by hepatorrhaphy (0.30 kg/cm2) and omental buttress (0.25 kg/cm2). Porcine WBS at 6 weeks after healing by second intent was significantly greater than WBS at 6 weeks after hepatorrhaphy or omental buttress. The canine WBS at 3 weeks after healing by second intent exceeded WBS at 3 weeks after hepatorrhaphy or omental buttress. Canine WBS at 6 weeks after healing by second intent exceeded WBS at 6 weeks after omental buttress and was similar to WBS at 6 weeks after hepatorrhaphy. WBS in all groups paralleled the extent of fibrosis seen on microscopic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of albumin resuscitation for shock on the immune response to tetanus toxoid.

A prior prospective random study showed that supplemental albumin led to a significant (P ⩽ 0.05) fall in immunoglobulin (Ig) content of IgG, IgM, and IgA; no measurement was made on the immune response to a known antigen. Therefore, the immune response to tetanus toxoid, measured by antibody precipitation, was studied in 43 nonalbumin patients and 22 albumin patients from whom frozen sera were available. The 65 patients received an average of 16 units blood during resuscitation and 0.5 ml tetanus toxoid. Using single radial immunodiffusion technique, duplicate double-blind measurements of precipitants formed by the patients tetanus toxoid antibody and purified tetanus toxoid (TTA) incorporated in 1% agarose gel were made. TTA levels in the 22 albumin patients were compared with all nonalbumin patients and with two subgroups of 22 patients—one randomly chosen; the other matched for number of transfusions. TTA was also correlated with time after injury. TTA was significantly less in albumin patients (215 ± 100 units) than in the nonalbumin patients (387 ± 233 units) and both subgroups of nonalbumin patients. TTA correlated directly with time after injury in the nonalbumin patients (slope = −0.4). Albumin resuscitation for shock results not only in a fall in Ig content but also a reduction in the immune response to tetanus toxoid.

The beneficial role of calcium supplementation during resuscitation from shock.

The role of calcium (Ca) in resuscitation from hemorrhagic shock is controversial and in the present report three regimens were compared: supplementation (Ca-S), avoidance (No-Ca), and Ca channel blockade (Ca-B). This was studied in 40 splenectomized dogs subjected to reservoir shock (MAP 60 torr/90 min, then 40 torr/30 min) and treated with: a) 20 ml/kg balanced electrolyte solution (BES); b) shed blood; c) 30 ml/kg BES; and d) 250 ml autologous bank blood. Three groups of six dogs received Ca-S (0.5 mEq/kg), No-Ca, or Ca-B (verapamil 0.15 mg/kg) in BES. Postoperative therapy of 50 ml/kg/d BES with Ca-S, No-Ca, or Ca-B was given for 3 days. The effects of parathyroidectomy (P) via wide thyroidectomy in 22 dogs treated with calphosan (20 ml/d) and L-thyroxin (0.02 mg/kg) preceding shock was also studied as above: Ca-S/P, No-Ca/P, and Ca-B/P; four sham dogs had anesthesia but no shock (Anes/P). Studies done before, during, and after shock and on day three included systemic pressures (MAP), central pressures (CFP), cardiac output (CO), resistance (SVR), heart work (LVW), and outcome. Post-resuscitation Ca was significantly less in all groups (1.6-3.7 mg%) compared to Ca-S (4.8 mg%). Compared to Ca-S dogs, the post-resuscitation studies in the No-Ca and Ca-B dogs showed lower MAP, CO, and LVW in both intact and hypoparathyroid animals. Post-resuscitation CFP was also lower in the Ca-S and Ca-S/P dogs compared to the other euparathyroid and hypoparathyroid dogs. Death after the initiation of resuscitation occurred in two No-Ca/P and three Ca-B/P dogs. These data suggest that calcium supplementation plus an intact calcium-parathyroid axis enhance the resuscitation effort.

Effect of albumin resuscitation on canine coagulation activity and content.

Prior work showed that albumin resuscitation in man leads to decreased coagulation activity and coagulation protein content. These observations were tested in 20 splenectomized dogs shocked by control hemorrhage and resuscitated with the sequential infusion of: (1) 20 ml/kg balanced electrolyte solution (BES) or 5% albumin/BES; (2) shed blood; (3) 30 ml/kg BES or 5% albumin/BES; (4) 250 ml blood stored from the time of splenectomy. Either BES or 5% albumin/BES was given for the next 3 days. Coagulation activity (fibrinogen, plasminogen, factor VIII, and prothrombin) and coagulation protein content (factor VIII by specific canine antigen) were measured preshock, post resuscitation, and daily for 3 days. Albumin resuscitation significantly (p = >0.05) reduced coagulation activity of fibrinogen (423 ± 145 vs. 274 ± 80 mg/dl SD), factor VIII:C (64 ± 24 vs. 42 ± 16% SD), prothrombin (195 ± 44 vs. 141 ± 22% SD) but did not alter CPC of factor VIII:RAg (142 ± 83 vs. 156 ± 141% SD). Lower coagulation activity after 5% albumin/BES resuscitation in conjunction with no change in factor VIII:RAg content which is produced by the vascular endothelium suggest that impaired hepatic synthesis may lead to the reduced coagulation activity after albumin resuscitation.

Wound Healing of the Injured Spleen With and Without Splenorrhaphy

Splenic wound healing was studied following splenorrhaphy and observational therapy for both canine and porcine splenic injury. The splenorrhaphy group included four adult male dogs and two adult male pigs studied 3 weeks postinjury. The observational therapy group included three dogs and three pigs examined at 3 weeks and three dogs and two pigs examined 6 weeks postinjury. The wound breaking strength (WBS) 3 weeks after splenorrhaphy was significantly greater than WBS of normal splenic tissue (0.41 vs. 0.71 kg/cm2 in dogs; 0.22 vs. 0.35 kg/cm2 in pigs). WBS 3 weeks after observant therapy for splenic injury in dogs was significantly less than normal (0.66 vs. 0.37 kg/cm2). No WBS differences were seen 3 weeks after observant therapy in pigs nor 6 weeks after observant therapy in dogs or pigs. Prolonged convalescence following splenic injury treated by repair or by observation appears unwarranted.

Relocation of nonalbumin proteins after albumin resuscitation

Prior work showed that albumin (5% A) resuscitation lowered serum globulins and coagulation protein activity levels compared to balanced electrolyte solution (BES) resuscitation. In this experiment, the effect of 1.25% A in BES (A-BES) on serum and lymphatic levels of nonalbumin proteins was studied in 20 splenectomized dogs subjected to reservoir shock and then treated with (a) BES or A-BES, (b) shed blood, and (c) autogenous bank blood. Serum levels of albumin, globulin, and coagulation protein activity were measured preshock, postshock, and daily for 3 days; skin lymph levels were measured on Day 3. Compared to BES, A-BES resuscitation significantly decreased serum globulins and coagulation protein activity of fibrinogen, Factor VIII, and antithrombin III. In contrast, skin lymph globulins and coagulation protein activity levels increased significantly with A-BES compared to BES resuscitation. These data suggest that the serum protein changes seen with albumin-supplemented resuscitation result from extravascular relocation of nonalbumin proteins, possibly, due to an oncotic homeostatic factor.