Catecholamine-resistant Hypotension Research Articles

Impact of Vasoplegic Syndrome on Early Clinical Outcome After Orthotopic Heart Transplantation

<h3>Purpose</h3> Vasoplegic syndrome (VS) is a possible complication after cardiac surgery using cardiopulmonary bypass (CPB) and is mainly characterized by a loss of systemic resistance leading to refractory hypotension and inadequate peripheral tissue perfusion. The objective of this retrospective study is to determine the impact of VS on short- and long-term morbidity and mortality after heart transplantation (OHT). <h3>Methods</h3> We retrospectively reviewed data of 156 consecutive adult patients who underwent OHT at our center between 2010 and 2021. VS was defined as persistent low systemic vascular resistance (<800 dynes/s/cm⁵) with preserved cardiac index (>2.5 L/min/m²) and catecholamine resistant hypotension despite intravenous vasopressors at a high dose (>0.2μg/kg/min norepinephrine) within the first 6-24 hours after surgery. Patients were divided into two groups classified by the presence or absence of vasoplegia. <h3>Results</h3> The incidence of VS was 11.5% (18 patients) with comparable donor and recipient characteristics in both groups. The mean age of vasoplegic patients was 51±10 (vs. 50±12) years and 88.9 % (vs.71.0%) were male. 61.6% (vs. 48.1%) had a history of prior cardiac surgery of which 44.4 % (vs. 28.1%) were implantations of left ventricular assist devices. Vasoplegic patients showed increased lactate levels at the end of CPB (9.0±5.3 vs. 4.9±3.1 mmol/L, p<.001) and higher rate of reoperation for bleeding (55,6% vs. 15.2% p<.001). Of the 18 vasoplegic patients, five patients (27.8%) received immediate mechanical circulatory support (MCS) at the end of CPB for a mean of 5±2.7 days, six patients (33.3%) received delayed MCS after a mean of 7.8±5.7 hours postoperatively for 6.1±4.6 days and seven patients (38.9%) were treated without MCS. 30-day survival rates were 100 % in patients receiving immediate MCS, 50% in patients with delayed MCS and 71.4% in patients without MCS, respectively. Overall 30-day survival rate was lower in vasoplegic patients (72.2% vs 94.9%, p<.001). If patients survived the first 30 days there was no significant difference in 1-year survival (92.3 % vs 90.2%). <h3>Conclusion</h3> Vasoplegic syndrome following heart transplantation was associated with increased perioperative 30-day mortality. Early MCS implantation seemed to be beneficial for short-term survival. Vasoplegic patients surviving the first 30 days had a comparable and good long-term outcome.

Hypotension and Brain Injury in Asphyxiated Newborns Treated with Hypothermia.

This study aimed to assess the incidence of hypotension in asphyxiated newborns treated with hypothermia, the variability in treatments for hypotension, and the impact of hypotension on the pattern of brain injury. We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. Mean blood pressures, lactate levels, and inotropic support medications were recorded during the hospitalization. Presence and severity of brain injury were scored using the brain magnetic resonance imaging (MRI) obtained after the hypothermia treatment was completed. One hundred and ninety term asphyxiated newborns were treated with hypothermia. Eighty-one percent developed hypotension. Fifty-five percent of the newborns in the hypotensive group developed brain injury compared with 35% of the newborns in the normotensive group (p = 0.04). Twenty-nine percent of the newborns in the hypotensive group developed severe brain injury, compared with only 15% in the normotensive group. Nineteen percent of the newborns presenting with volume- and/or catecholamine-resistant hypotension had near-total injury, compared with 6% in the normotensive group and 8% in the group responding to volume and/or catecholamines. Hypotension was common in asphyxiated newborns treated with hypothermia and was associated with an increased risk of (severe) brain injury in these newborns.

Hypotension following Patent Ductus Arteriosus Ligation: The Role of Adrenal Hormones

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0μg/kg) stimulation test (performed before the ligation), and at 10-12hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1×dopamine [μg/kg/min]+1×dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P=.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production.

Vasopressin for the Treatment of Neonatal Hypotension

Vasopressin (pitressin), also known as arginine vasopressin (AVP), is an antidiuretic hormone formed in the hypothalamus and secreted from the posterior pituitary gland. Various forms of exogenous vasopressin exist and have been used in neonates to treat conditions such as diabetes insipidus. Vasopressin has also been studied on a limited basis for use in the treatment of catecholamine-resistant hypotension in vasodilatory shock. Hypotension is a significant problem resulting in increased morbidity in preterm, septic, and postsurgical neonates. This article will discuss the role of vasopressin and its use as a therapeutic agent in the treatment of hypotension in the neonate.

Effects of terlipressin on pulmonary artery pressure in a septic cooled infant: an echocardiographic assessment

Experience with terlipressin (TP) in the neonatal field is scarce. We describe the effects of TP on pulmonary circulation, studied with echocardiography, in an asphyxiated septic cooled infant with pulmonary hypertension (PH) who developed catecholamine-resistant hypotension and exacerbation of PH shortly after the beginning of the rewarming. TP was added to norephinephine and adrenaline infusions at the dose of 0.02 mg kg(-1) every 6 h, because of refractory hypotension and oliguria. After 10 min, blood pressure dramatically and definitely increased, and urinary output was re-established after 60 min. Echocardiographic evaluation 30 min after the second bolus of TP showed unchanged velocity of the tricuspidal valve regurgitation and improved biventricular functional indexes respect to the pre-treatment assessment. TP was continued for 12 h (three doses) without significant adverse effect except for a transient increase in troponin levels. Addition of TP boluses to catecholamine infusion in our newborn was effective in increasing systemic vascular resistance without increasing pulmonary vascular resistance, successfully reversing the hemodynamics of severe PH, and suggesting a potential primary vasodilator effect on pulmonary circulation. Transient increase of troponin levels during TP treatment confirms the risk of excessive coronary vasoconstriction when TP boluses are added to high dose catecholamines.

The response to methylene blue in patients with severe hypotension during liver transplantation

Methylene blue is a useful therapy for catecholamine-resistant vasoplegic shock. Three cases of methylene blue administration for the treatment of catecholamine-resistant hypotension during orthotopic liver transplantation are presented.

Vasopressin for the treatment of catecholamine-resistant hypotension during a phaeochromocytoma resection in a 6-year-old child

Vasopressin for the treatment of catecholamine-resistant hypotension during a phaeochromocytoma resection in a 6-year-old child

Terlipressin as Rescue Therapy in Catecholamine-Resistant Hypotension in Solid Organ Donors: A Case Report

Objective The objective of this study was to report the effects of Terlipressin treatment in 2 potential organ donors with intractable, catecholamine-resistant hypotension. Design and Setting This study was based on case reports in the intensive care unit of a general hospital. Patients Patients included 2 adult patients with cerebral death and catecholamine-resistant hypotension. Interventions A low dose of Terlipressin (3.5 μg/kg) by intravenous bolus was added to the standard treatment. Measurement and Results In both cases, Terlipressin induced a rapid improvement in arterial pressure with a consequent increase in urine output and the appearance of diabetes insipidus. In 1 patient it allowed for the withdrawal of norepinephrine infusion. No related adverse effects were detected in either patient. Organ removal was not possible in the second case due to lack of family consent. Conclusions Terlipressin might be considered as a rescue therapy for potential organ donors with intractable, catecholamine-resistant hypotension. In spite of the positive results obtained here and by other authors in the treatment of septic shock, its judicious use is recommended, and an optimal administration schedule must still be elucidated.

Effects of low dose vasopressin in catecholamine resistant septic shock

Background: Septic shock commonly leads to death in critically ill patients. Severe hypotension resistant to conventional catecholamine leads to multiorgan failure. We studied the effectiveness of low dose vasopressin in resistant septic shock. Methods: Thirty critically ill patients with catecholamine resistant hypotension were included in the study. After adequate fluid resuscitation, infusion of norepinephrine and dobutamine was started. If the patient remained hypotensive, vasopressin was infused at a fixed rate of 0.04 unit/minute for 24 hours. Haemodynamic parameters and mortality rates were recorded. Result: There was a significant improvement in systolic and mean arterial pressure within four hours of starting vasopressin. This improvement continued throughout the 24-hour period. In addition, it was possible to withdraw dopamine in all the patients and significantly reduce infusion rates of dobutamine and norepinephrine. No significant complication was noted. Conclusion: Low dose vasopressin at the rate of 0.04 unit/minute is an effective vasopressor in adult patients with catecholamine resistant septic shock.

Vasopressin in paediatric practice

Arginine vasopressin (AVP) is a nine amino acid peptide hormone, which is synthesized in the hypothalamus as a precursor, transported down the portal system and stored in the posterior pituitary gland. It is also known as argipressin or antidiuretic hormone (ADH) and it is closely related in structure to oxytocin, which is also released from the posterior pituitary. Physiologically, it acts though the kidney with several other hormones to conserve solute-free water, but in hypovolemic states its potent arterial and venoconstrictor properties act to preserve blood pressure. Vasopressin has been used for many years in the treatment of diabetes insipidus and in control of bleeding esophageal varices (utilizing its potent vasoconstrictor effect on the slanchnic circulation), but its role as a pressor agent in the context of resuscitation, septic shock and pediatric cardiac surgery has only emerged in the last few years. Vasopressin is released physiologically in response to a rise in osmolarity, which is sensed within sensitive receptors in the hypothalamus. A fall in osmolarity below 280 mOsmAEkg will trigger its release (1). It acts via V2 receptors to open aquaporin (water channels) in the collecting tubules thereby increasing central water reabsorption. Reduction in afferent transmission from baroreceptors or cardiopulmonary volume receptors associated with hypovolemia or hypotension will also trigger vasopressin release which then acts via V1a receptors of smooth muscle to produce vasoconstriction of both veins and arteries (2). Similarly, increases in circulating ANG11 act via the hypothalamus to trigger release (3). The vasoconstictive effects are specific to different organ beds with the slanchnic bed being particularly sensitive to the circulating concentrations of vasopressin. In addition, increase in vasopressin activity is associated with increased release of corticotrophin releasing hormone via V1b (V3) receptors within the CNS, an increase in release of FV111, Von Willebrand Factor and enhanced platelet aggregation. The physiological effects on the heart are unclear. In the isolated healthy myocyte AVP produces improved contractility (4) probably by increasing intracellular calcium in myocardial cells through a GTP mechanism (5): The integrated position is less clear: pharmacological doses cause coronary vasoconstriction, while improved inotropic performance in pathological states may occur due both primary myocardial effect of secondary effects because of improved coronary perfusion. Pathologically, vasopressin is known to rise in heart failure and conditions of cardiovascular compromise. There are less data in children: in a study of neonates with congenital heart disease, AVP levels in infants with congestive heart and no outflow tract obstruction was significantly higher than normal controls but those with failure and left ventricular outflow tract obstruction had reduced levels (6). The available data suggest that while vasopressin levels are often raised appropriately in hypotensive states because of a variety of conditions this is not necessarily the case. Small studies have been published documenting vasopressin deficiency in catecholamine resistant hypotension (7,8). Vasopressin became of interest when it was observed that organ donors who had brain death and diabetes insipidus were cardiovascularly more stable with reduced inotrope requirements and better organ preservation. Additionally, it was observed that patients who survived cardiac arrest had higher levels of vasopressin compared to nonsurvivors (9). In contrast, there is a correlation of poorer outcome after cardiopulmonary resuscitation with higher levels of endogenous catecholamines (10). These observations led to initial adult studies which questioned whether the purer vasoPediatric Anesthesia 2008 18: 579–581 doi:10.1111/j.1460-9592.2008.02520.x

Insufficient Vasopressin Release From Adequate Pituitary Stores Contributes to Inappropriately Low Plasma Vasopressin Levels in the Acute Response to Septic Shock

Inadequate endogenous vasopressin (eVP) levels have been well described in catecholamine resistant hypotension in the setting of septic shock. In a piglet model of endotoxin (ETX) induced septic shock, we examined possible mechanisms for why eVP may not achieve adequate levels to reverse hypotension. eVP response to a 37% decrease in mean arterial pressure achieved levels of 150 ± 10 pg/mL (n=45) which were not sufficient to raise blood pressure. Plasma VP (pVP) levels achieved with pharmacologically administered vasopressin (VP) at 1, 10, and 100 ng/kg/min revealed that pVP levels of at least 400 pg/mL were needed to reverse hypotension (p&lt;0.05). For piglets given ETX, pituitary levels of VP were measured and found to still contain adequate stores (735 ± 51 ng/pit) although decreased from non‐ETX controls (1297 ± 290 ng/pit) . Next we examined whether eVP could be further released by other stimuli in the face of endotoxic hypotension. Dopamine was infused in piglets who had the same degree of hypotension as untreated controls and was found to further increase pVP to 203.5 pg/mL ± 34.5, p&lt;0.02. Given these results it appears that the pituitary has the stores and the capacity to release more eVP in septic shock. The mechanism responsible for low levels of pVP therefore seems to be due at least in part to the inability of the pituitary to adequately release the hormone in response to endotoxin‐induced hypotension.

Use of Vasopressin Bolus and Infusion to Treat Catecholamine-resistant Hypotension during Pheochromocytoma Resection

Albert Einstein Medical Center, Philadelphia, Pennsylvania. rothj@einstein.eduIn a recent review of vasopressin, it was stated that there were only two reported cases using bolus vasopressin (10–20 U) to restore blood pressure after pheochromocytoma resection.1This letter documents another rare case, using a lower dose of bolus vasopressin, for treatment of catecholamine-resistant hypotension after pheochromocytoma resection.A 54-yr-old man (height, 180 cm; weight, 84 kg) underwent laparoscopic right adrenalectomy for treatment of pheochromocytoma. Preoperative medications included phenoxybenzamine, metoprolol, ramipril, and atorvastatin. Preinduction blood pressure was 129/74 mmHg, and heart rate was 57 beats/min. During manipulation of the adrenal gland, the patient developed hypertension, which was treated with sodium nitroprusside (up to 10 ml/h of 200 μg/ml) and esmolol (up to 5 ml/h of 10 mg/ml) infusions. After resection and discontinuation of the nitroprusside and esmolol, the patient developed hypotension. A norepinephrine infusion of 24 μg/min was only able to increase the patient's systolic blood pressure to the low to mid 80s. Two 0.4-U vasopressin boluses were administered, which increased the systolic blood pressure to 120 mmHg. The patient was started on a 4-U/h infusion of vasopressin resulting in maintenance of a systolic blood pressure at 110 mmHg while permitting a decrease in the norepinephrine infusion rate. Both infusions were continued throughout the rest of the surgery and were weaned several hours postoperatively. The patient did well and was discharged home on postoperative day 2.There are now three previous reports of bolus vasopressin being used to treat hypotension after adrenal resection for pheochromocytoma.2–4Repeated bolus doses of 10–20 U followed by an infusion were required to treat hypotension after pheochromocytoma resection.2In another adult patient, an infusion of vasopressin required 20 min to achieve improvement in blood pressure during pheochromocytoma resection complicated by a large blood loss.3In an 11-yr-old patient, a 5-U bolus followed by an infusion was successful in treating postresection hypotension.4Although vasopressin infusions have been used in a variety of other situations, there are limited data to guide bolus dosing. Others report lower doses of vasopressin bolus. A 2-U bolus dose was used to treat anaphylactic shock.5As in this case, two 0.4-U boluses successfully treated hypotension secondary to both bowel retraction in patients having abdominal aortic resection repair and postreperfusion syndrome during liver transplantation.6,7Terlipressin (a vasopressin precursor) in doses of 1 or 2 mg successfully treated hypotension secondary to induction of anesthesia in patients chronically treated with renin–angiotensin system inhibitors.8Additional well-controlled studies must be conducted to establish the indications, safety, and efficacy of bolus vasopressin for rapid correction of hypotension, particularly catecholamine-resistant hypotension.This patient adds to the small number of reported cases that suggest vasopressin can be safely and effectively used to treat postadrenalectomy catecholamine-resistant hypotension in patients with pheochromocytoma. Although vasopressin is a vasoconstrictor and it is not surprising that it can treat hypotension, there may be a specific need for vasopressin in some pheochromocytoma patients. First, vasopressin is effective in the presence of residual α-adrenergic blockade and down-regulation of those receptors. Second, in some patients with pheochromocytoma, there is an oversecretion of vasopressin, which may contribute to the induced hypertension.9,10It is possible that chronic oversecretion of vasopressin leads to a down-regulation of vasopressin receptors, thus contributing to the postresection hypotension. Whether preoperative determination of vasopressin over secretion will affect management is an open question. Catecholamines are also known to inhibit vasopressin release.11It has been proposed that chronic inhibition by catecholamines may down-regulate neurohypophyseal vasopressin synthesis, thereby preventing the acute high release of vasopressin during a hypotensive episode.2Last, the use of vasopressin can reduce the catecholamine dose, thus allowing one to avoid their undesirable side effects such as increased myocardial oxygen consumption and ventricular arrhythmias.Albert Einstein Medical Center, Philadelphia, Pennsylvania. rothj@einstein.edu

Peripheral Administration of Vasopressin for Catecholamine-Resistant Hypotension Complicated by Skin Necrosis

Peripheral Administration of Vasopressin for Catecholamine-Resistant Hypotension Complicated by Skin Necrosis

Peripheral Administration of Vasopressin for Catecholamine-Resistant Hypotension Complicated by Skin Necrosis

To the Editor:The Surviving Sepsis Campaign entered its second phase last year with the publication of guidelines for management of severe sepsis and septic shock. One of the recommendations is that a vasopressin infusion (0.01–0.04 units/min) should be considered in patients with refractory shock d

Vasopressin in the treatment of vasodilatory shock in children

Many recent studies suggest that vasopressin deficiency is an important cause of catecholamine-resistant hypotension with vasodilation in adults, but little is known about vasopressin deficiency in children. To clarify the usefulness of vasopressin administration in pediatric cathecolamine-resistant hypotension with preserved ventricular contractility, urinary output and blood pressure response to vasopressin were retrospectively analyzed in 12 consecutive patients (15 instances) who were treated with vasopressin. The causes of vasodilation were central nervous system disturbance (n = 5), side-effect of drug (n = 5), and infection (n = 5). Plasma vasopressin concentration was measured six times before vasopressin administration and five times during vasopressin administration. Patients were divided into four groups according to their response to vasopressin administration. In group 1 (n = 5), urinary output increased to > 3 mL/kg per h within 3 h after vasopressin administration. In group 2 (n = 4), urinary output increased to > 3 mL/kg per h from 3 to 5 h after vasopressin administration. In group 3 (n = 4), urinary output did not increase to > 3 mL/kg per min within 5 h after vasopressin administration, but systolic blood pressure increased to > 120% of the level at the time of vasopressin administration. All remaining patients were classified into group 4 (n = 3). Plasma vasopressin concentration were low considering the markedly hypotensive state in all six instances. Plasma vasopressin concentration during vasopressin administration were significantly increased compared with before administration (P < 0.05). No apparent side-effects were observed in this series. Vasopressin deficiency may occur in catecholamine-resistant hypotension of pediatric patients due to various causes including central nervous system disturbance, drug induced hypotension and sepsis. Small doses of vasopressin administration seems to be very effective in such conditions by increasing blood pressure and urinary output.

Therapy for vasodilatory shock: Arginine vasopressin

V ASODILATORY SHOCK is a condition of hypotension with end-organ hypoperfusion resulting from a decrease in systemic vascular resistance. This vasodilatory state is a well-known characteristic of septic shock, but it is also observed in the late phase of hemorrhagic shock and as a complication of cardiopulmonary bypass. 1-3 Catecholamine vasopressors, the only clinically used vasoconstrictors, can be effective, but their action is frequently diminished in vasodilatory shock, and side effects are prominent at increased doses. ~-4 Thus, the morbidity and mortality from catecholamine-resistant hypotension in vasodilatory shock remains high, and alternative treatments could be useful. The mechanisms responsible for vasodilation in the various syndromes associated with vasodilatory shock continues to be elucidated. We and others have shown that the vasodilatory shock of sepsis is mediated in part by vasodilatory mechanisms such as the inappropriate release of nitric oxide (NO) and the opening of adenosine triphosphate (ATP)-sensitive potassium channels (K+ATP) on vascular smooth muscle. 56 The possibility that vasoconstrictor mechanisms, such as arginine vasopressin (AVP), might be defective and thus contribute to vasodilatory shock has not been as well studied. Our incidental observation of a marked vasopressor response to exogenous AVP in a patient with vasodilatory septic shock contrasted with the decreased effectiveness of catecholamine vasoconstrictors in this patient. This led us to examine the role of AVP in the hypotension of vasodilatory shock. We discovered that the baroreflex-mediated secretion of vasopressin is defective not only in septic shock but in a variety of vasodilatory shock

SURGICAL OPERATION OF 12 PATIENTS WITH PSYCHIATRIC DISEASE

In a 4-year period from April, 1988 to March, 1992, we performed surgical operation for 12 patients with psychiatric disease. There were 8 men and 4 women, with an average age of 56.5 years. These patients have been troubled with various psychiatric diseases, such as shizophrenia in 7 cases, dementia, mania and depression, Parkinson's disease, mental disorder by methanphetamine and alcholism in each one case, for 3 months to 35 years before the operation. Operations were performed emergently in 5 cases (41.7%) and under general anesthesia in 10 cases (83.3%), Catecholamine-resistant hypotention, suspected to be induced by long-term medication of antipsychotic drugs, was observed in 5 cases (41.7%) in the period of intra-and postoperative stages. Antipsychotic drugs were given until the day before operation, and restarted with meals in all cases. However strange and disquieting behaviors were observed in 6 cases (50%) postoperatively, all of them could be discharged from the hospital with recovery of their surgical diseases. In the management of surgical psychiatric patients, causion should be exersized to the possible occurrence of intra-and postoperative catecholamine-resistant hypotension.