· I.
;I
- - -I . ~II CHEST editorials -=-
~
Was a Magic Bullet Aimed In the Right Direction? Ina randomized, double-blind, placebo-controUed multicentered trial, Bone et a1l demonstrated that prostaglandin E l (pGE.) failed to reduce mortality in postoperative and medical patients with ARDS. In the present issue, Silverman et al (see page 405) of this group describe the long-term effects of this agent on oxygen delivery (Do.), oxygen consumption (Yo.), and oxygen extraction (01 ext) in a subset of 37 of these patients who had received PGEI for six days or more. They concluded that this agent improved Doll and VOl' even though this did not lead to improved outcome. In the accompanying editorial to the first article, Jenkinsonll concluded that PGE I was not the magic bullet that improves survival in patients with ARDS . However, Silverman's studies differed substantially from the earlier studies that treated first with Huid therapy the circulatory problems of postoperative shock, ie, low or maldistributed flow that was inadequate to supply the increased metabolic demands reflected by high VOIl . 3•• Before accepting Jenkinson's conclusion, it might be appropriate to ask if the bullet was pointed in the right direction. In the studies of Bone et all and Silverman et al the VOl and DOs in the PGEI group averaged only 136 and about 500 mIl minemll, respectively, which is considerably below the 170 and 600 mIlmineml values empirically observed in critically ill survivors.' Even though they increased 001 , the optimal goals were not achieved except in the nonsurvivor group after four days; under these conditions, increased metabolism is more likely due to late complications, principally sepsis. The authors failed to realize that the primary problem in postoperative shock and shock-related organ failure is tissue hypoxia and oxygen debt from inadequate or maldistributed flow and blood volume.Y In earlier PGEI studies," volume therapy was first given to correct as much as possible the tissue hypoxia from postoperative or traumatic shock; then PGEI was added to further improve oxygen transport variables. If the action of PGE I is to inhibit platelet and neutrophil activation by the deleterious effects of thromboxane, it would seem appropriate first to correct as much as possible the tissue hypoxia to prevent the continued generation of more thromboxane by the
VOlUME 98 I NUMBER 2 I AUGUST, 1990
cyclooxygenase mechanism. PGE I should be considered as ancillary therapy, not as a substitute for optimal Huid administration. . In the studies by Bone et all and Silverman et al, changes in were closely associated with comparable changes in VOs in most of their patients. An alternative conclusion might be that oxygen requirements had not been met and that further increases in VOs would have resulted from additional increases in Doll as have been demonstrated with fluid therapy.3,ll Bone et all and Silverman et al have clearly shown that PGE I improves, but does not optimize oxygen transport variables in the inadequately fluid-loaded surgical patient. They mayor may not have fired a magic bullet, but the real question is whether they expended it in the most effective fashion. William C. Shoemaker, M.D.
Dos
Los Angeles
Martin Luther Jang Jr.ICharies R. Drew MedicalCenter. REFERENCES
1 Bone RC, Slotman G, Maunder R, Silverman R, Ryeo TM , Kerstein MD, et al. Randomized double-blind,multicenter study «prostaglandin E. In pdienb with the adult respiratory distress syndrome. Chest 1989;96:114-19 2 Jenkinson SG. ProstlIgLmdin E.: Not the magic bullet In ARDS. Chest 1989;96:1-2 3 Shoemaker WC, Appel PL, i'Rm RD, Wuman K, Lee T-S. ProspectiYe trla1 «supnoormaI values« survivors as therapeutic pJs In highrisk mrgicaI patienb. Chest 1988; 9f:1176-86 4 Shoemaker WC, Appel PL . Etrects «prostagIandm E. In adult respiratory dUtress syndrome. SIU"pr)' 1986; 99:275-S3 5 Shoemaker WC , Appe1 PL, i'Rm RD . 11ssue oxygen debt as a determmant «1etIW and oooIetbaI pOStDptliative 0I'gaD failure. Crit Care Med 1988; 16:1117-20 6 Shoemaker WC, i'Rm RD. EfFects crystalloids and ooUoids on hemodynamics, oxygen transport, and outrome in high-risk surgical patients. In: Slmmoos RC, Udekuo AS, eels. Debates In c1InicaI surgery. Chicago: Yearbook, 1990; 1:263-302
«
Classification of Immediate-type, Llf8-threatenlng Allergic or PseudoaIlerglc ReactIons
H oman anaphylaxis is a medical emergency re-
quiring immediate therapy. Although episodes
ofanaphylaxis may have spontaneous recovery, the risk
of fatality is such that immediate therapy should be QEST I ll8 I 2 I AlJGUSl; 19110
217
;I
- - -I . ~II CHEST editorials -=-
~
Was a Magic Bullet Aimed In the Right Direction? Ina randomized, double-blind, placebo-controUed multicentered trial, Bone et a1l demonstrated that prostaglandin E l (pGE.) failed to reduce mortality in postoperative and medical patients with ARDS. In the present issue, Silverman et al (see page 405) of this group describe the long-term effects of this agent on oxygen delivery (Do.), oxygen consumption (Yo.), and oxygen extraction (01 ext) in a subset of 37 of these patients who had received PGEI for six days or more. They concluded that this agent improved Doll and VOl' even though this did not lead to improved outcome. In the accompanying editorial to the first article, Jenkinsonll concluded that PGE I was not the magic bullet that improves survival in patients with ARDS . However, Silverman's studies differed substantially from the earlier studies that treated first with Huid therapy the circulatory problems of postoperative shock, ie, low or maldistributed flow that was inadequate to supply the increased metabolic demands reflected by high VOIl . 3•• Before accepting Jenkinson's conclusion, it might be appropriate to ask if the bullet was pointed in the right direction. In the studies of Bone et all and Silverman et al the VOl and DOs in the PGEI group averaged only 136 and about 500 mIl minemll, respectively, which is considerably below the 170 and 600 mIlmineml values empirically observed in critically ill survivors.' Even though they increased 001 , the optimal goals were not achieved except in the nonsurvivor group after four days; under these conditions, increased metabolism is more likely due to late complications, principally sepsis. The authors failed to realize that the primary problem in postoperative shock and shock-related organ failure is tissue hypoxia and oxygen debt from inadequate or maldistributed flow and blood volume.Y In earlier PGEI studies," volume therapy was first given to correct as much as possible the tissue hypoxia from postoperative or traumatic shock; then PGEI was added to further improve oxygen transport variables. If the action of PGE I is to inhibit platelet and neutrophil activation by the deleterious effects of thromboxane, it would seem appropriate first to correct as much as possible the tissue hypoxia to prevent the continued generation of more thromboxane by the
VOlUME 98 I NUMBER 2 I AUGUST, 1990
cyclooxygenase mechanism. PGE I should be considered as ancillary therapy, not as a substitute for optimal Huid administration. . In the studies by Bone et all and Silverman et al, changes in were closely associated with comparable changes in VOs in most of their patients. An alternative conclusion might be that oxygen requirements had not been met and that further increases in VOs would have resulted from additional increases in Doll as have been demonstrated with fluid therapy.3,ll Bone et all and Silverman et al have clearly shown that PGE I improves, but does not optimize oxygen transport variables in the inadequately fluid-loaded surgical patient. They mayor may not have fired a magic bullet, but the real question is whether they expended it in the most effective fashion. William C. Shoemaker, M.D.
Dos
Los Angeles
Martin Luther Jang Jr.ICharies R. Drew MedicalCenter. REFERENCES
1 Bone RC, Slotman G, Maunder R, Silverman R, Ryeo TM , Kerstein MD, et al. Randomized double-blind,multicenter study «prostaglandin E. In pdienb with the adult respiratory distress syndrome. Chest 1989;96:114-19 2 Jenkinson SG. ProstlIgLmdin E.: Not the magic bullet In ARDS. Chest 1989;96:1-2 3 Shoemaker WC, Appel PL, i'Rm RD, Wuman K, Lee T-S. ProspectiYe trla1 «supnoormaI values« survivors as therapeutic pJs In highrisk mrgicaI patienb. Chest 1988; 9f:1176-86 4 Shoemaker WC, Appel PL . Etrects «prostagIandm E. In adult respiratory dUtress syndrome. SIU"pr)' 1986; 99:275-S3 5 Shoemaker WC , Appe1 PL, i'Rm RD . 11ssue oxygen debt as a determmant «1etIW and oooIetbaI pOStDptliative 0I'gaD failure. Crit Care Med 1988; 16:1117-20 6 Shoemaker WC, i'Rm RD. EfFects crystalloids and ooUoids on hemodynamics, oxygen transport, and outrome in high-risk surgical patients. In: Slmmoos RC, Udekuo AS, eels. Debates In c1InicaI surgery. Chicago: Yearbook, 1990; 1:263-302
«
Classification of Immediate-type, Llf8-threatenlng Allergic or PseudoaIlerglc ReactIons
H oman anaphylaxis is a medical emergency re-
quiring immediate therapy. Although episodes
ofanaphylaxis may have spontaneous recovery, the risk
of fatality is such that immediate therapy should be QEST I ll8 I 2 I AlJGUSl; 19110
217
