% vol = 17 number = 4 prevlink = 185 nextlink = 193 titolo = "HYPERTENSIVE URGENCIES ASSOCIATED WITH MAJOR BURNS" volromano = "XVII" data_pubblicazione = "December 2004" header titolo %>
SUMMARY. Despite the common occurrence of the complication in extensive body burns of hypertensive urgencies, which may even become true hypertensive emergencies during the treatment of paediatric burns, few data are available on hypertensive complications during the treatment of major burns in adults. To our knowledge, no article addressing the hypertensive urgencies that may occur during the treatment of burn injury in adults has been published in the literature. This article presents our clinical experience in the treatment of eight adult major burn patients who developed post-burn hypertensive urgency, and the clinical characteristics of the cases are discussed. Some possible physiological determinants are suggested for the increased systemic blood pressure in burn patients. We recommend antihypertensive drugs that restore vascular endothelium’s vasoactive functions as the drug of choice in the treatment of hypertensive urgencies after major burns.
Hypertension complicating thermal injury has been reported by various authors in the literature.1,2 Systemic hypertension may appear as a common complication during the treatment of major paediatric burns.3,4 An extensive body burn is also reported as one of the causes of hypertensive urgencies, which may even become true hypertensive emergencies.5 Despite the reported common occurrence of this complication during the treatment of paediatric burns, few data are available referring to hypertensive complications during the treatment of major burns in adults. Molteni et al. reported that 49 out of 193 adult patients with second- and third-degree burns involving more than 25% of the total body surface area (TBSA) developed a hypertensive urgency within three to four days of admission.6 To our knowledge, no other article addressing the hypertensive urgencies that may occur during the treatment of burn injury in adults has been published in the literature. This article presents our clinical experience in the treatment of eight adult major burn patients who developed post-burn hypertensive urgency, and the clinical characteristics of the cases are discussed. Some possible physiological determinants are suggested for the increased systemic blood pressure in burn patients.
As we have faced first hypertensive urgencies during the early phase of treatment of major burn patients, a prospective study was undertaken to document the certain laboratory determinants of well-known causes of secondary hypertension in major burn patients associated with hypertensive urgencies.
During the last year, the arterial blood pressure of all adult patients admitted with major burn injury was screened for hypertensive urgencies during the acute phase of their treatment. Patients in whom the total second- and third-degree burns exceeded 25% TBSA were judged to be major burn cases, requiring hospitalization and resuscitation. Twenty-four out of a total of 30 major burn patients, who survived for more than two weeks, were included in the study, while six patients who died within the first 15 of injury were excluded. Arterial blood pressures were monitored and recorded, beginning on the first day after admission. Hypertension was decided on the basis of increased systolic and diastolic pressure above 140/90 mm Hg. Mean arterial pressure (MAP) was calculated as follows: MAP = diastolic pressure + 1/3 (systolic-diastolic pressure). Patients in whom elevated arterial blood pressure was detected were additionally screened for serum aldosterone levels, plasma renin activity, and T3, T4, TSH, ACTH, and cortisol levels. Urinary cortisol and vanyl-mandelic acid were also examined. Serum electrolytes (Na and K levels) and fluid balance were recorded daily and fluid balance was calculated as total fluid intake minus total fluid output.
All the patients were adults (mean age, 37 yr) suffering from major burn injuries (mean TBSA, 43% second- and third-degree burns). Hypertension was diagnosed in eight of the 24 patients (33%). In all patients, a hypertensive urgency appeared during the acute phase of the burn injury. A brief summary of each case is given below (Table I) and the results of the measurements are presented in Table II.<% createTable "Table I ","A brief summary of each case",";Case; Sex; Age (yr); Admission day post-burn ;Aetiology; % TBSA; Additional injuries and pre-morbid disorders; Surgical intervention treatments; Reason of mortality; Timing of mortality; Hospital stay of surviving patients@;1; M; 33; 2; High voltage; 30; Excision and grafting Excision, and left grafting below-knee and below-elbow amputations 80 days @;2; M; 41; 4; Flame;40; -;Inhalation injury Sepsis and MOF ;Day 20; -@;3; M; 20; 3; High voltage; 35;-; Right below-knee and bilateral below-elbow amputations;-;-; 60 days@;4; M; 44; 3; Flame; 40; -;Haemodialysis Acute renal failure, sepsis and MOF; Day 16;-@;5; F; 32; 5; Flame; 38; -;Tangential excision and grafting; -;-; 25 days@;6; F; 52; 1; High voltage; 58;-; Bilateral above-knee amputations;-;-; 30 days@;7; F; 18; 3; Flame; 44; -; Mechanical ventilation ARDS; -; 45 days@;8; M; 58; 8; Flame; 64 ; Invasive infection and sepsis; Day 17 ;-","",4,300,true %> <% createTable "Table II ","Neuroendocrine and electrolyte assays in blood and urine samples. Normal laboratory values: free T3: 2.3-4.2 pg/ml; free T4: 0.89-1.76 pg/dl; TSH: 0.35-5.5 mIU/ml; aldosterone: 8-172 pg/ml; plasma renin activity: 0.2-2.8 ng/ml; vanyl mandelic acid (VMA): 0-6.5 mg/24 h; ACTH: 0-46 pg/ml; urine cortisol: 28-213.7 mg/24 h; serum Na: 135-145 mEq/l; serum K: 3.5-5.0 mEq/l",";Case;Na; K; Plasma renin activity; Aldosterone; ACTH; T3; T4; TSH; Urine cortisol; VMA; Net fluid balance@;1; 136.0; 4.27; 0.3; 25.4; 10; 1.88; 2.25; 2.43; 85; 3.4; +1380.5@;2; 147.2; 3.31; 0.3; 58.9; 176; 1.54; 1.03; 0.56; 150; 1.4; +3322.2@;3; 139.1; 4.50; 1; 25; 37.5; 2.34; 0.66; 0.96; 95; 1.8; +2173.3@;4; 138.5; 4.34; 0.3; 79.2; 287; 1.24; 1.07; 4.61; 78; 1.5; +1685.7@;5; 139.4; 3.81; 0.5; 28.9; 155; 1.66; 1.02; 0.32; 54; 1.7; +1155.4@;6; 142.8; 4.67; 0.9; 26.8; 27; 1.33; 1.02; 2.76; 23; 2.0; +1788.5@;7; 145.5; 4.02; 0.7; 59.6; 43; 1.45; 0.67; 3.01; 43; 1.5; +1780.5 @;8; 146.4; 3.97; 0.4; 34.5; 305; 2.01; 0.76; 4.01; 67; 2.8; +2500","",4,300,true %>
The aetiological agent of the burn injury was flame only in three of the eight patients who developed a hypertensive urgency, while three of the cases were major burns due to high voltage injury (38%). Despite our efforts, three of the patients died, respectively on days 16, 17, and 20 post-injury. A lethal outcome could not be prevented in the patient with associated inhalation injury. Acute renal failure due to inadequate resuscitation before the patient’s referral to our centre, leading to sepsis and subsequent multiple organ failure, was the reason for the mortality of the patient with high-voltage injury, while methicillin-resistant Staphylococcus aureus sepsis due to inappropriate burn wound management and the patient’s late referral resulted in mortality in the third case. Blood-pressure data pertaining to each patient are given as diagrams plotted to observe the changes, so as to reveal the effectiveness of our treatment (Figs. 1-8).
|<% immagine "Fig. 1","gr0000032.jpg","Blood pressure monitoring and drug therapy results in case 1. N = Level of hypertension, 140/90 mm Hg.",230 %>||<% immagine "Fig. 2","gr0000033.jpg","Blood pressure monitoring and drug therapy results in case 2. N = level of hypertension, 140/90 mm Hg.",230 %>|
|<% immagine "Fig. 3","gr0000034.jpg","Blood pressure monitoring and drug therapy results in case 3. N = level of hypertension, 140/90 mm Hg.",230 %>||<% immagine "Fig. 4","gr0000035.jpg","Blood pressure monitoring and drug therapy results in case 4. N = level of hypertension, 140/90 mm Hg.",230 %>|
|<% immagine "Fig. 5","gr0000036.jpg","Blood pressure monitoring and drug therapy results in case 5. N = level of hypertension, 140/90 mm Hg.",230 %>||<% immagine "Fig. 6","gr0000037.jpg","Blood pressure monitoring and drug therapy results in case 6. N = level of hypertension, 140/90 mm Hg.",230 %>|
|<% immagine "Fig. 7","gr0000038.jpg","Blood pressure monitoring and drug therapy results in case 7. N = level of hypertension, 140/90 mm Hg.",230 %>||<% immagine "Fig. 8","gr0000039.jpg","Blood pressure monitoring and drug therapy results in case 8. N = level of hypertension, 140/90 mm Hg.",230 %>|
The overall incidence of hypertension in childhood burns has been reported by different researchers to range from 20 to 89%.2-4, 7 Although it is known as a common complication of thermal injury in the paediatric age group, the only article addressing hypertension during the treatment of thermal injury in adults was published by Molteni et al.6 in 1979, who reported an incidence of 25%. To the best of our knowledge, the present preliminary report is only the second to consider post-burn hypertensive urgencies in adults.
Despite the reported clinical data indicating that hypertension is a common complication after burn injury in the paediatric age group, little is known about the underlying pathophysiological mechanisms. In order to elucidate the underlying pathophysiology of hypertension that appears during the treatment of major burns, we investigated in our cases some well-known aetiological indicators of systemic hypertension. The patients were screened for certain serum and urine parameters related to common causes of secondary hypertension. The results of the neuroendocrine assays did not yield any valuable data to justify a hypertensive urgency. Also, serum electrolyte determinations did not indicate any significant change that might explain the hypertension in any of the patients. The mean values for the net fluid balance seemed to be high, but no significant difference was evident when compared with burn index matched normotensive patients. In short, we were unable to obtain any finding that offered a reasonable causative explanation for the hypertension in our cases.
Experimental data obtained from studies on vascular reactivity and systemic haemodynamic changes in thermal injury have revealed that major burn injury is associated with decreased systemic vascular resistance and increased pulmonary vascular resistance.8 Systemic hypotensive tendency in acute burns has been reported to be due to vasodilator substances such as histamine, bradykinin, PGE2, and PGF2a released from the burn wound,9 while it has been suggested that increased pulmonary vascular resistance results from internalization of vasoactive-substance receptors and alterations in calcium influx into the smooth muscle cells.10 This explanation for the underlying mechanism of increased pulmonary vascular resistance implies a lack of target organ response to vasoactive substances. Only a lack of target organ response can justify the increased vascular resistance or hypertensive complications despite the abundance of circulating vasodilator substances in major burn injuries. Hence, a pathophysiological mechanism based on “target organ dysfunction” seems reasonable for hypertensive urgencies associated with major burn injuries.
Burn wound infection and ensuing sepsis (host response to infection) are common and mostly inevitable complications associated with major burns. Recent studies have revealed that endothelial cells play a key role in the pathogenesis of sepsis, and a microvascular endothelial dysfunction has been suggested as the underlying mechanism of sepsis related organ dysfunctions.11 In major burns, even the extensive nature of thermal injury alone can trigger a systemic inflammatory response syndrome (SIRS) that may lead to death with progression to multiple organ failure (MOF) like sepsis. With or without infection, they are similar, with a common pathophysiology, severe systemic inflammation, the target of which is known to be vascular endothelial cells. In major burns, what causes MOF is known to be vascular endothelial damage caused by severe systemic inflammation.
What happens in major burns can be described as follows - major burns trigger a systemic inflammatory response (SIRS), in which the main target of the activated leucocytes is the vascular endothelium. The endothelial damage caused by these activated leucocytes is thought to result in organ dysfunctions, with a lethal outcome in major burn injuries. Considering the available knowledge on the pathophysiological mechanisms of major burns and SIRS, we can assume that all major burn injuries are inevitably associated with a varying degree of systemic endothelial dysfunction. Vascular endothelium is known to exert a very important blood pressure regulatory role by releasing both relaxing and contracting factors and modulating vascular smooth muscle tone.12 In the early stage of thermal injury, intact endothelium is deemed to cause arterial vasodilatation by endothelium-dependent and nitric oxide (NO)-mediated smooth vascular muscle relaxation.
Another point that cannot be overlooked is that the aetiology in the majority of major burn cases associated with hypertensive urgencies is high-voltage electrical injury. This may be attributed to the relative susceptibility of blood vessels to electricity. Jaffe et al. described the loss of vessel endothelium following electrical injury.13 Also, during the acute phase of burn injury, burn toxins interfere with the vasoactive functions of the endothelium with an enhanced vasoconstrictor and diminished vasodilator response.13,15,16 It may be assumed that the widespread endothelial dysfunction or damage occurring in our patients was due to both the electrical injury and the cutaneous burns.
In modern antihypertensive treatment, drugs are chosen on the basis of their ability to reverse impaired endothelium-dependent functions.17 In three of our patients, antihypertensive treatment was initiated with a beta blocker drug. Since we were unable to achieve the desired response with the first treatment, an angiotensin-converting enzyme inhibitor (ACE-I) was added to the treatment protocol as a second drug, yielding a satisfactory antihypertensive effect. In the rest of the patients, an angiotensin II (AT-II) receptor antagonist drug was used as a single-drug treatment protocol with a favourable antihypertensive response.
It has been demonstrated that ACE inhibitor drugs improve endothelial dysfunction by restoring NO availability.16 Also, AT-II receptor antagonists restore the endothelium-dependent vasodilatation achieved by acetylcholine, improve basal NO release, and decrease the vasoconstrictor effect of endogen endothelin-1.17,18 The positive effect of ACE-I and AT-II antagonist drugs on vascular endothelium might have enhanced their antihypertensive success in our burn patients and, if that is so, this may support the idea that post-burn hypertension may at least in part be due to widespread endothelial dysfunction.
Post-burn hypertensive complications are seldom seen in adults, compared to the situation in children. We agree with studies stating that there are no proven clinical data demonstrating a systemic reason for such hypertensive cases after major burns. Considering post-burn hypertensive urgencies as essential may therefore be a reasonable inference. Additionally, endothelial dysfunction could be assumed to be the underlying mechanism. In conclusion, we recommend antihypertensive drugs that restore vascular endothelium’s vasoactive functions as the drug of choice in the treatment of hypertensive urgencies after major burns.
RESUME. Malgré la fréquence chez les grands brûlés de la complication des urgences hypertensives, qui peuvent se transformer en de véritables émergences hypertensives pendant le traitement des brûlures pédiatriques, la littérature offre peu de données sur les complications hypertensives pendant le traitement des grands brûlés adultes. A la connaissance des Auteurs, il n’existe aucun article qui s’occupe des urgences hypertensives qui peuvent se manifester pendant le traitement des brûlures chez les adultes. Après avoir présenté leur expérience clinique dans le traitement de huit grands brûlés qui ont manifesté une urgence hypertensive post-brûlure et discuté les caractéristiques cliniques des cas, ils avancent une possible hypothèse physiologique pour la tension systémique augmentée chez les patients brûlés. Ils concluent en recommandant l’emploi des médications antihypertensives qui restaurent les fonctions vasoactives de l’endothélium vasculaire comme la médication de premier choix dans le traitement des urgences hypertensives à la suite des brûlures graves.