Email updates

Keep up to date with the latest news and content from Critical Care and BioMed Central.

Open Access Research

Low systemic vascular resistance: differential diagnosis and outcome

Jairo Melo1 and Jay I Peters2

Author Affiliations

1 Department of Medicine, Division of Pulmonary Diseases/Critical Care Medicine, The University of Texas Health Science Center at San Antonio, Texas, USA

2 The South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, San Antonio, Texas, USA

For all author emails, please log on.

Critical Care 1999, 3:71-77  doi:10.1186/cc343


The electronic version of this article is the complete one and can be found online at: http://ccforum.com


Received:11 January 1999
Revisions received:10 May 1999
Accepted:11 May 1999
Published:9 June 1999

© 1999 Current Science Ltd

Abstract

Objective

To determine the frequency and prognosis of the various causes of low systemic vascular resistance (SVR).

Design

Analysis of consecutive patients over a 5-year period; retrospective review.

Setting

Medical intensive care unit of a large university hospital.

Patients

Fifty-five patients with unexplained hypotension and a SVR less than 800 dynes × s/cm5.

Background

There are minimal data in the medical literature determining the frequency or outcome of patients with a low SVR that is unrelated to sepsis or the sepsis syndrome. We retrospectively reviewed and analyzed all hemodynamic data in a large university hospital over a 5-year period to determine the frequency and prognosis of the various causes of low SVR. Fifty-five patients with unexplained hypotension and a SVR less than 800dynes×s/cm5were identified.

Main results

Twenty-two patients (Groups 1 and 2) met the criteria for sepsis syndrome. The mean SVR for this group was 445 ± 168 dynes×s/cm5 with an associated mortality of 50%. Group 3 contained 20 patients with possible sepsis. Thirteen patients (Group 4) were nonseptic. The mean SVR of this group was 435 ± 180 dynes × s/cm5 with an associated mortality of 46%. Extremely low SVR (below 450 dynes × s/cm5) was associated with a significantly higher mortality regardless of the etiology.

Conclusions

At least a quarter of patients with hypotension and a low SVR have nonseptic etiologies. The patients with nonseptic etiologies have a similar mortality to septic patients. Clinicians should be aware of the wide spectrum of conditions that induce a low SVR.

Keywords:
adrenal insufficiency; anaphylaxis; cirrhosis; hypotension; pancreatitis; sepsis; systemic vascular resistance

Introduction

As initially described by Poiseuille's law, resistance to flow is that resistance provided by a vessel or circulatory bed which permits a given pressure differential to produce a unit flow. Transcribed to human hemodynamics, systemic vascular resistance (SVR) can be measured from the differential pressure between the mean arterial pressure (MAP) and the central venous pressure (CVP) divided by the flow, ie cardiac output (CO). Although many clinical conditions can cause a low SVR, septic shock remains the most common cause and usually results in a severe decrease in SVR. In more than 90% of patients with septic shock who are aggressively volume loaded, the CO is initially normal or elevated. Therefore, hypotension results from reduced vascular resistance with normal or elevated CO. This form of shock results from maldistribution of blood flow to tissues, usually from acute vasodilatation without concomitant expansion of the intravascular volume. While distributive shock can also be caused by anaphylaxis, drug ingestion, neurogenic injury, and adrenal insufficiency, these conditions are seen with less frequency in the intensive care unit. Therefore, a hemodynamic state with low SVR is often considered synonymous of sepsis, and other conditions associated with a low SVR may not be considered.

There are minimal data in the medical literature assessing the frequency or outcome of patients with distributive shock that is unrelated to sepsis or the sepsis syndrome. Since we could find no prior studies in the literature assessing the etiology and outcome of hypotensive patients with a low SVR, we reviewed our experience with patients undergoing hemodynamic monitoring in the medical intensive care unit of a large university hospital. The purpose of this study was to determine the different causes of low SVR, identify prognostic factors, and analyze the mortality of these various groups of patients.

Methods

After approval by the Institutional Review Board of the University of Texas Health Science Center at San Antonio, medical records of all patients admitted to the medical intensive care unit of the University Hospital between 1990–1995 were reviewed. All the charts of patients undergoing pulmonary artery catheterization were identified. Patients with a recorded SVR less than 800 dynes ×s/cm5 were analyzed. The main indication for pulmonary artery catheterization in patients in this study was unexplained hypotension after volume challenge. Any patient with an unclear etiology for hypotension or any patient requiring more than 10 μ g/kg/min dopamine underwent pulmonary artery catheterization and was reviewed for this study. Anxiolytics, sedatives, and neuromuscular blocking agents are administered by protocol and have minimal or no direct effects on hemodynamics or histamine release. Cultures of blood and urine were obtained on all patients; cultures of sputum, pleural fluid, ascitic fluid, and cerebrospinal fluid were obtained as clinically indicated. Toxicological screening of blood and urine for drugs was performed on admission if the etiology of hypotension was in question. Serum cortisol level determination was performed on all patients receiving exogenous corticosteroids or in patients with known risk factors for adrenal insufficiency. Hematologic and blood chemistry determinations, arterial blood gases, routine urinalysis, and serial electrocardiograms were obtained on all patients.

Mean systemic, right atrial, and pulmonary artery pressures and thermodilution cardiac outputs were measured every 4 h in all patients. Derived hemodynamic variables were calculated as follows: cardiac index (CI; l/min/m2) = CO/body surface area; SVR (dynes × s/cm5)=(80× MAP)/CO; and systemic vascular resistance index (SVRI)=SVR/body surface area. Patients received vasopressors to maintain MAP above 70 mmHg. The set of hemodynamic data with the lowest SVR was selected for each patient.

All historical, clinical, laboratory, microbiologic, and hemodynamic data were studied. Patients were divided into four groups based on the following parameters: (1) positive blood culture; (2) temperature ≥ 38.1°C or ≤ 36°C; (3) white blood counts (WBCs) ≥ 12000/mm3 or ≤ 4000/mm3; and (4) obvious source of infection. Group 1 (definite sepsis) had positive blood cultures and two or more criteria; Group 2 (probable sepsis) had an obvious source of infection and two or more additional criteria; Group 3 (possible sepsis) had fever and leukocytosis or leukopenia with no obvious source of infection nor positive blood culture; and Group 4 (nonseptic) had none of the criteria.

The clinical course, laboratory findings, hemodynamics, and intensive care unit mortality were compared between the various groups. Data are expressed as mean ± standard deviation. Clinical and hemodynamic variables were compared with a student's t-test and by analysis of variance to assess statistical significance between groups. Logistic regression analysis was performed comparing SVR and death using a univariant analysis.

Mortality was assessed by Mann-Whitney rank sum test. A P value of ≤ 0.05 was considered statistically significant.

Results

Fifty-five patients were included in the study (Table 1). Group 1 contained 18 patients with definite sepsis; Group 2 contained four patients with probable sepsis; Group 3 contained 20 patients with possible sepsis; and Group 4 contained 13 patients who had no evidence of sepsis. The mean age of the patients was 50 ± 13.6years. Thirty-four patients were men, and 21 patients were women. The overall MAP was 72 ± 20 mmHg at the moment the hemodynamic values were chosen. The overall mean CO was 9.2 ± 6.18l/min, and the mean CI was 5.1 ± 1.7l/min/m2. The overall mean SVR was 435 ± 180 dynes × s/cm5; the mean SVRI was 785 ± 325 dynes × s/cm5. Analysis of SVRI was reviewed for each subgroup and not found to be different from the analysis of SVR; therefore, only data for SVR are presented.

There were no statistically significant differences in age, sex, or admission temperature among the different groups. Twenty-two patients (Groups 1 and 2) met the criteria for the sepsis syndrome [1]. The mean SVR was 445 ± 168 dynes × s/cm5, CO was 10.86 ± 5.22l/min; and CI was 5.08 ± 1.64l/min/m2 for this group. The overall mortality in those patients classified as having the sepsis syndrome was 50%. In patients with the sepsis syndrome, the lung was the primary site of infection in 14 out of 22 patients. Thirteen patients were considered nonseptic (Group 4). This group had no source of infection, alteration in temperature, leukocytosis, or leukopenia. The mean hemodynamic values for this group were: SVR = 435 ± 180 dynes × s/cm5; CO = 9.23 ± 4.24l/min, and CI = 7.72 ± 1.9l/min/m2. The mortality was 46%. There were no statistically significant differences in any hemodynamic values nor in mortality between the nonseptic group (Group 4) and the groups with sepsis syndrome (Groups 1 and 2). The nonseptic group included eight patients with intra-abdominal disease (five with decompensated cirrhosis, three with acute pancreatitis), one patient with adrenal insufficiency, and four patients with unclear etiologies for hypotension and low SVR (idiopathic). The mortality in patients with decompensated intra-abdominal disease was 75% (six out of eight). Additionally, no statistically significant difference in any of the hemodynamic values or mortality was identified between the four groups when analyzed individually (Table 2).

Twenty-seven patients met the criteria for the extreme hyperdynamic state (EHS). In the literature [2], EHS is defined as an SVR below 450 dynes × s/cm5 and a CO above 7l/min/m2. The mean hemodynamic values for patients in this study with EHS were: SVR = 327± 85 dynes × s/cm5; CO = 12.13 ± 3.31l/min; and CI = 5.98 ± 1.46 l/min/m2. Seven of these patients had a diagnosis of underlying cirrhosis. Twelve of the patients within this group were diagnosed with sepsis syndrome, 10 with possible sepsis, and five were nonseptic. This group had a statistically significant higher mortality (60% versus 33%) than those patient without the EHS (P < 0.05). A univariant logistic regression was performed analyzing the level of reduction of SVR and mortality. A statistically significant relationship was found between these variables (P = 0.025). For every reduction in SVR of 50dynes × s/cm5, there was a 20% increase in mortality (odds ratio = 1.2; range = 1.022-1.434).

Table 1. Clinical parameters of study groups

Discussion

Sepsis and sepsis syndrome were the most common etiologies of a low SVR in this study. Although many studies have found urinary or intra-abdominal sepsis to be the most common cause of low SVR [3], the lung was the primary site of infection in over half of our patients.

Septic shock, the leading cause of intensive care unit mortality, is caused by systemic activation of the inflammatory cascade. Numerous mediators, including cytokines, kinins, complement, coagulation factors, and eicosanoids, are activated or systematically released, resulting in profound disturbances of cardiovascular and organ system function. These mediators, particularly tumor necrosis factor (TNF), interleukin (IL)-1, platelet activating factor, and prostaglandins, are thought to mediate the reduced peripheral vascular resistance seen in septic shock [4,5,6].

Parker et al [7] studied serial cardiovascular variables in humans with septic shock. A low SVR was seen in both survivors and nonsurvivors; however, persistently low SVR beyond 24 h was a strong predictor of mortality. This study demonstrated that the majority of patients (65%) who die of septic shock have a persistently low SVR, while a smaller percentage die of low CO (10%) or of multiple organ failure (25%) after hemodynamic resolution of shock. Although we did not evaluate serial hemodynamic profiles in this study, our data identify a group of patients with EHS who demonstrate a SVR below 450 dynes × s/cm5 and a mean CO over 12l/min. As with patients in prior studies [2], this group demonstrated a significantly higher mortality. Although the mechanisms relating to the difference in mortality are unknown, it has been suggested that patients with "complicated" shock (defined as multiorgan failure) have greater distortions of cardiorespiratory patterns relative to the degree of hypotension and that this is associated with a higher mortality [8,9]

Our study demonstrates that patients with sepsis syndrome are the most common group of patients presenting with hypotension and a low SVR in the medical intensive care unit. This group only represents approximately 40% of patients in our study. While many of the remaining patients had some evidence supporting the diagnosis of sepsis (eg fever, leukocytosis), they lacked an identifiable source of infection, and the exact etiology of their hypotension remains unknown. More significantly, almost one-quarter of the patients (24%) in this study developed hypotension and a low SVR without any evidence of sepsis. This group had a high mortality (46%), similar to the remaining patients (54%). There were no significant differences in the clinical or hemodynamic parameters between the nonseptic patients and the patients in the remaining groups. The frequency of nonseptic causes of a low SVR suggest that clinicians must be aware of conditions other than sepsis that have either been well documented (Table 3) or reported to induce a reduction in the SVR (Table 4).

The largest group of nonseptic patients in this study with hypotension and a low SVR was found to be patients with decompensated cirrhosis. Although occult infections should not be excluded, none of these patients had fever, leukocytosis, an identifiable site of infection, or abnormalities in the peritoneal fluid. Patients with liver cirrhosis often present with systemic hemodynamic disturbances, including hypotension, low SVR, and a reduced sensitivity to vasoconstrictors [10]. The precise mechanisms of these hemodynamic disorders have not yet been clearly elucidated. Excessive production of vasodilators, peripheral shunts, and increased levels of nitric oxide in these patients may contribute to the hyperdynamic state observed in this population [10,11,12,13,14,15,16]. A recent study by Matsumoto [16] demonstrated that patients with decompensated liver cirrhosis had higher levels of exhaled nitric oxide than patients with compensated cirrhosis, chronic liver disease, or controls. The decompensated cirrhotics had a significantly higher CO and a lower SVR than the compensated patients. Additionally, a positive correlation was found between the level of nitric oxide and CI. Five of our patients with a low SVR had decompensated liver disease as the presumed etiology of their hypotension. Another five patients in the possible sepsis group had hypotension with a clinical diagnosis of spontaneous bacterial peritonitis; however, the lack of positive cultures, or any other evidence of infection, suggest that decompensated liver disease may have played a significant role in their hypotension.

Pancreatitis was found to be the second most common cause of low SVR in patients without evidence of infection. Three patients had necrotizing pancreatitis, with one of these having evidence of hemorrhage into the pancreas. Hemodynamic manifestations of pancreatitis include a normodynamic or hypodynamic state, usually present in acute interstitial pancreatitis and commonly associated with hypovolemia. Pancreatitis can also present as a hyperdynamic state with high CO and a low SVR as described by Di Carlo et al [17] and Bradley et al [18]. This hyperdynamic state is another manifestation of the severity of acute pancreatitis and is seen mostly in necrotizing pancreatitis with or without hemorrhage [19]. Severe pancreatitis may mimic sepsis syndrome or septic shock despite the absence of any infectious site. The mechanisms responsible for pancreatic shock have not been elucidated; however, an inflammatory cascade generalized by cytokines and TNF is felt to be the most likely cause of this process [17,18,19].

Adrenal insufficiency was found in one of our patients with no evidence of infection. Unfortunately, cortisol levels and adrenocorticotrophic hormone (ACTH) response was not routinely measured in patients with infection, and adrenal insufficiency may have been underestimated in this group. Adrenal insufficiency may present as a hypodynamic, normodynamic, or hyperdynamic state [20]. The hypodynamic state is usually seen early in adrenal insufficiency and is associated with volume depletion from diarrhea, vomiting, and decreased reabsorption of sodium in the distal tubule. CO may also be decreased in adrenal insufficiency as the result of the myofibrillar adenosine triphosphate (ATP) depletion seen with glucocorticoid deficiency [20]. Intravenous fluid therapy most often increases CO and decreases SVR in patients with adrenal crisis. These patients are usually separated from patients with sepsis by a baseline cortisol level below 10μ g/dl or an inadequate response to ACTH [20]. One of our patients with septic shock had baseline cortisol of 22μ g/dl and no response to the cosyntropin stimulation test. This patient could not be weaned off high dose norepinephrine and dopamine until intravenous corticosteroids were instituted. Normal values for basal and stimulated cortisol levels are derived from the adrenal response of healthy individuals. Patients experiencing the severe stress of critical illness demonstrate higher than normal amounts of circulating cortisol. Some patients with critical illness have minimal or no ACTH stimulation above their baseline cortisol levels and may be unable to respond to additional physiologic stress [20]. Several reports suggest a significant number of critically ill patients may have unrecognized adrenal insufficiency [21,22,23,24].

Four cases of idiopathic hypotension with low SVR were identified in our patients. One case was felt to be related to possible anaphylaxis or anaphylactoid reaction but was not well documented. Silverman et al [25] reported a patient who developed anaphylactic shock secondary to penicillin 7days postmyocardial infarction; the hemodynamic parameters showed a decrease in CO and MAP with an increase in SVR. Moss et al [26] reported the opposite hemodynamic profile in a patient with anaphylactic shock secondary to succinycholine. Their patient developed a low SVR and a high CO which correlated with increased levels of histamine and catecholamines. Although there are minimal human data, animal studies suggest there is an initial hypodynamic state secondary to severe extravasation of fluids into the tissues followed by a hyperdynamic state after fluid resuscitation.

Our second case of hypotension with a low SVR presented in the setting of an acute myocardial infarction. Although cardiogenic shock presents with a high SVR and low CO, some data suggest that, rarely, patients may present with a syndrome of low SVR. McCriskin et al [27] reported a patient with a left ventricular pseudoaneurysm postmyocardial infarct with a low SVR and no evidence of infection. Costantin [28] developed an animal model in dogs and demonstrated a subset of animals with a hyperdynamic state after coronary occlusion; however, Ross et al [29] were unable to confirm these results using another animal model. Similarly, Smith et al [30], in one of the original hemodynamic descriptions of patients after myocardial infarction, did not identify any patient with a hyperdynamic state. Another recently described cause of low SVR in cardiac patients is the "vasoplegic syndrome". This syndrome occurs within 6h after cardiac surgery using extracorporeal circulation [31]. The incidence has been estimated between 0.4 and 5% of patients undergoing cardiovascular surgery using cardiopulmonary bypass [31,32]. The etiology is unclear but has not been associated with increased levels of nitric oxide or endotoxin.

One patient with a low SVR classified as idiopathic had a history of significant alcohol consumption. Their initial hemodynamic parameters showed a low SVR with high CO which rapidly resolved after intravenous thiamine and broad-spectrum antibiotics. It is possible that this case represents a variant of beriberi heart disease. This rare but treatable disease should be considered in every patient with congestive heart failure and a low SVR. The fulminant form known as Shosin beriberi presents as a high CO state with extremely high CO and a low SVR which rapidly responds to thiamine [33,34,35].

The remaining patient in the idiopathic group had no explanation for their low SVR syndrome. Review of the literature shows many causes of a low SVR (Tables 3 and 4), and it is possible that one of these diagnosis was missed by the clinicians caring for this patient. The patient had normal urine drug abuse screens and a normal serum acetaminophen level. A salicylate level was not obtained. Leatherman and Schmitz [36] reported a series of five patients who became accidentally intoxicated with salicylates with clinical, laboratory, and hemodynamic features of sepsis, but without bacteriological evidence. In two of the cases, TNF-α, IL-1 and IL-6 were measured and found to be significantly elevated. Other drugs have been associated with a low SVR including tricyclic antidepressants, anesthetic agents, and narcotics. Recently Nguyen et al [37] reported hyperdynamic shock caused by trimethoprim-sulfamethoxazole in which immunoglobulin E antibodies and TNF were not detected and complement levels were normal, suggesting a mechanism other than anaphylaxis. Our drug screen should have identified tricyclic antidepressants or narcotics in the urine; however, a careful drug history was not elicited in this patient. Although other conditions such as head injury [38,39,40], Paget's disease [41,42,43], arteriovenous fistula [44], severe anemia [45,46], multiple myeloma [47], thyrotoxicosis [48], and spinal cord injury [49] have been reported to produce a low SVR, this patient lacked any clinical evidence suggesting one of these diagnoses; his hypotension resolved spontaneously.

Table 2. Mean hemodynamic values and mortality (± SD)a

Table 3. Documented conditions associated with low SVR

Table 4. Conditions reported to have low SVR

Conclusion

In summary, we describe a group of 55 patients with a SVR below 800dynes×s/cm5, and a subgroup of 13 non-septic patents (24%) with a similar mortality. This study emphasizes the importance of considering other conditions besides sepsis in patients presenting with hypotension and a low SVR.

References

  1. Bone RC, Balk RA, Cerra FB, et al.: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee, American College of Chest Physicians/Socity of Critical Care Medicine.

    Chest 1992, 101:1644-1655. PubMed Abstract OpenURL

  2. Baumgartner JD, Vaney C, Perret C: An extreme form of they hyperdynamic syndrome in septic shock.

    Int Care Med 1984, 10:245-249. OpenURL

  3. Winslow E, Loeb H, Rahimtoola S, et al.: Hemodynamic studies and results of therapy in 50 patients with bacteremic shock.

    Am J Med 1973, 54:421-432. PubMed Abstract OpenURL

  4. Parillo JE, Parker MM, Natanson C, et al.: Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy.

    Ann Intern Med 1990, 113:227-242. PubMed Abstract OpenURL

  5. Parillo JE, Burch C, Shelhamer JH, et al.: A circulating myocardial depressant substance in humans with septic shock.

    J Clin Invest 1985, 6:1542-1553. OpenURL

  6. Weber KT, Ratshin RA, Janicki JS, et al.: Left ventricular dysfunction following acute myocardial infarction.

    Am J Med 1973, 54:697-705. PubMed Abstract OpenURL

  7. Parker M, Shelhamer JH, Natanson C, et al.: Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis.

    Crit Care Med 1987, 15:923-929. PubMed Abstract OpenURL

  8. Shoemaker WC, Mohr PA, Printen KJ, et al.: Use of sequential physiologic measurements as guides in therapy of uncomplicated septic shock.

    Surg Gynecol Obstet 1970, 131:245-254. PubMed Abstract OpenURL

  9. Shoemaker WC: Cardiorespiratory patterns in complicated and uncomplicated septic shock: physiologic alterations and their therapeutic implications.

    Ann Surg 1971, 174:119-125. PubMed Abstract OpenURL

  10. Moller S, Henriksen JH: Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects.

    Semin Nephrol 1997, 17:505-519. PubMed Abstract OpenURL

  11. Sherlock S: Vasodilatation associated with hepatocellular disease: relation to functional organ failure.

    Gut 1990, 31:365-367. PubMed Abstract OpenURL

  12. Fernandez-Rodriguez CM, Prieto J, Zozaya JM, et al.: Arteriovenous shunting, hemodynamic changes, and renal sodium retention in liver cirrhosis.

    Gastroenterology 1993, 104:1139-1145. PubMed Abstract | Publisher Full Text OpenURL

  13. Lewis FW, Adair O, Rector W: Arterial vasodilation is not the cause of increased cardiac output in cirrhosis.

    Gastroenterology 1992, 102:1024-1029. PubMed Abstract | Publisher Full Text OpenURL

  14. Smith REA, Robinson NMK, McPeake JR, et al.: Induction and role of NO synthase in hypotensive hepatic failure.

    Arterioscler Thromb Vasc Biol 1997, 17:3079-3082. PubMed Abstract | Publisher Full Text OpenURL

  15. Friedman HS, Fernando H: Ascites as a marker for the hyperdynamic heart of Laennec's cirrhosis.

    Alcohol Clin Exp Res 1992, 16:968-970. PubMed Abstract OpenURL

  16. Matsumoto A: Increased nitric oxide in the exhaled air of patients with decompensated liver cirrhosis.

    Ann Intern Med 1995, 123:110-113. PubMed Abstract | Publisher Full Text OpenURL

  17. Di Carlo V, Nespoli A, Chiesa R, et al.: Hemodynamic and metabolic impairment in acute pancreatitis.

    World J Surg 1981, 5:329-339. PubMed Abstract OpenURL

  18. Bradley EL, Hall JR, Lutz J, et al.: Hemodynamic consequences of severe pancreatitis.

    Ann Surg 1983, 198:130-133. PubMed Abstract OpenURL

  19. Beger HG, Bittner R, Buchler M, et al.: Hemodynamic data pattern in patients with acute pancreatitis.

    Gastroenterology 1986, 90:74-79. PubMed Abstract | Publisher Full Text OpenURL

  20. Bouachour G, Tirot P, Varache N, et al.: Hemodynamic changes in acute adrenal insufficiency.

    Int Care Med 1994, 20:138-141. OpenURL

  21. Baldwin WA, Allo M: Occult hypoadrenalism in critically ill patients.

    Arch Surg 1993, 128:673-676. PubMed Abstract OpenURL

  22. Sibbald WJ, Short A, Cohen MP, et al.: Variations in adrenocortical responsiveness during severe bacterial infections.

    Ann Surg 1977, 186:29-33. PubMed Abstract OpenURL

  23. Finlay WEI, McKee JI: Serum cortisol levels in severely stressed patients.

    Lancet 1982, 1:414-1415. OpenURL

  24. Claussen MS, Landercasper J, Cogbill TH: Acute adrenal insufficiency after trauma and surgery.

    J Trauma 1992, 31:94-100. OpenURL

  25. Silverman HJ, Van Hook C, Haponik EF: Hemodynamic changes in human anaphylaxis.

    Am J Med 1994, 77:341-344. OpenURL

  26. Moss J, Fahmy NR, Sunder N, et al.: Hormonal and hemodynamic profile of an anaphylactic reaction in man.

    Circulation 1981, 63:210-213. PubMed Abstract OpenURL

  27. McCriskin JW, Baisden CE, Spaccevento LJ, et al.: Pseudosepsis after myocardial infarction.

    Am J Med 1987, 83:577-579. PubMed Abstract OpenURL

  28. Costantin L: Extracardiac factors contributing to hypotension during coronary occlusion.

    Am J Cardiol 1963, 205-217. PubMed Abstract OpenURL

  29. Ross J, Frahm CJ, Braunwald E: The influence of intracardiac baroreceptors on venous return, systemic vascular volume and peripheral resistance.

    J Clin Invest 1961, 40:563-572. OpenURL

  30. Smith W, Wikler NS, Fox AC: Hemodynamic studies of patients with myocardial infarction.

    Circulation 1954, 9:352-362. PubMed Abstract OpenURL

  31. Gomes WJ, Carvalho AC, Palma JH, et al.: Vasoplegic syndrome after open heart surgery.

    J Cardiovasc Surg 1998, 39:619-623. OpenURL

  32. Myles PS, Leong CK, Currey J: Endogenous nitric oxide and low systemic vascular resistance after cardiopulmonary bypass.

    J Cardiothorac Vasc Anesth 1997, 11:571-574. PubMed Abstract OpenURL

  33. Ayzenbert O, Silber MH, Bortz D: Beriberi heart disease: a case report describing the haemodynamic features.

    S Afr Med J 1985, 68:263-265. PubMed Abstract OpenURL

  34. Pereira VG, Masuda Z, Katz A, et al.: Shoshin beriberi: report of two successfully treated patients with hemodynamic documentation.

    Am J Cardiol 1984, 53:1467. PubMed Abstract OpenURL

  35. Kawai C, Wakabayashi A, Matsumura T, et al.: Reappearance of beriberi heart disease in Japan: a study of 23 cases.

    Am J Med 1980, 69:383-386. PubMed Abstract OpenURL

  36. Leatherman JW, Schmitz PG: Fever, hyperdynamic shock, and multiple-system organ failure: a pseudosepsis syndrome associated with chronic salicylate intoxication.

    Chest 1991, 100:1391-1396. PubMed Abstract OpenURL

  37. Nguyen B, Landucci DL, Cunnion RE, et al.: A case of hyperdynamic shock caused by trimethoprim-sulfamethoxazole in which no tumor necrosis factor or features of anaphylaxis were detected.

    Clin Infect Dis 1993, 17:885-887. PubMed Abstract OpenURL

  38. Brown RS, Mohr PA, Carey JS, et al.: Cardiovascular changes after cranial cerebral injury and increased intracranial pressure.

    Surg Gynecol Obstet 1967, 125:1205-1211. PubMed Abstract OpenURL

  39. Brown RS, Shoemaker WC: Sequential hemodynamic changes in patients with head injury: evidence for an early hemodynamic defect.

    Ann Surg 1973, 177:187-192. PubMed Abstract OpenURL

  40. Clifton GS, Robertson CS, Kyper K, et al.: Cardiovascular response to severe head injury.

    J Neurosurg 1983, 59:447-454. PubMed Abstract OpenURL

  41. Henley JW, Croxson RJ, Ibbertson HK: The cardiovascular system in Paget's disease of bone and the response to therapy with calcitonin and diphosphonate.

    Aust N Z J Med 1979, 9:390-397. PubMed Abstract OpenURL

  42. Sgrnberger CF, Smedal MI: The mechanism and incidence of cardiovascular changes in Paget's disease (osteitis deformans): a critical review of the literature with case studies.

    Circulation 1952, VI:711-726. OpenURL

  43. Lequime J, Denolin H: Circulatory dynamics in osteitis deformans.

    Circulation 1955, 12:215-219. PubMed Abstract OpenURL

  44. Sanyal S, Saldivar V, Coburn TP, et al.: Hyperdynamic heart failure due to A-V fistula associated with Wilms' tumor.

    Pediatrics 1976, 57:564-567. PubMed Abstract OpenURL

  45. Brannon ES, Merrill AJ, Warren JV, et al.: The cardiac output in patients with chronic anemia as measured by the technique of right atrial catheterization.

    J Clin Invest 1945, 24:332-336. OpenURL

  46. Varat MA, Adolph RJ, Fowler NO: Cardiovascular effects of anemia.

    Am Heart J 1972, 83:415-446. PubMed Abstract OpenURL

  47. McBride W, Jackman JD Jr, Gammon RS, et al.: High output cardiac failure in patients with multiple myeloma.

    N Engl J Med 1988, 319:1651-1653. PubMed Abstract OpenURL

  48. Goldman S, Olajos M, Morkin E: Control of cardiac output in thyrotoxic calves.

    J ClinInvest 1984, 73:358-365. OpenURL

  49. Tator CH: Review of experimental spinal cord injury with emphasis on the local and systemic circulatory changes .

    Neurochirugie 1991, 37:291-302. OpenURL