Catecholamine-resistant Septic Shock Research Articles

EFFICACY OF NOVEL SYNTHETIC ANGIOTENSIN II IN SEPTIC SHOCK

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Septic shock is a form of distributive shock characterized by decreased organ perfusion secondary to a dysregulated host response to infection. Septic shock has been associated with life-threatening multiple organ dysfunction and staggering mortality, with some studies estimating mortality greater than 50%. One of the cornerstones of improving outcomes has been maintaining adequate mean arterial pressure with vasopressors. Preliminary trials have shown that synthetic angiotensin II, a novel category of vasopressors which acts directly on the renin-angiotensin-aldosterone system, has significant vasopressor effect with no significant difference in serious adverse effects. Our study examined the effects of synthetic angiotensin II as a third-line agent in septic shock, comparing the change in MAP three hours after initiation, lactate clearance three hours after initiation, length of ICU stay, and cost. METHODS: We conducted a retrospective cohort study examining patients with septic shock on two vasopressors, with catecholamine-resistant shock (total catecholamine dose requirement >0.2 mcg/kg/min), requiring the initiation of a third agent. We compared patients who received synthetic angiotensin II versus a control group of any other appropriate third-line vasopressor. The protocol was approved by the IRB at Orange Regional Medical Center and data was obtained from the charts of ICU patients at the same hospital. RESULTS: There was a statistically significant increase in MAP at three hours in the angiotensin II group compared to the control group (16.3 mmHg vs. 4.3 mmHg; p = 0.0304). Overall, lactic acid clearance at 3 hours in the angiotensin II group was better than in the control group (13.39% vs. -57.2%), but was not statistically significant (p = 0.1338). Length of ICU stay did not statistically differ between the groups (433.6 hours vs 402.9 hours; p = 0.8370). Cost was significantly higher in the angiotensin II group versus the control group ($5717.84 vs. $1267.21; p < 0.0001). CONCLUSIONS: In our study of patients with catecholamine-resistant septic shock, initiation of synthetic angiotensin II as a third-line agent showed a significant improvement in MAP at 3 hours compared to other traditional third-line agents, without improvement in lactate clearance or ICU length of stay and at significantly higher cost. While showing promise as a potent vasopressor, given that angiotensin II has not yet demonstrated significant reductions in length of ICU stay, duration of mechanical ventilation, or mortality, the cost effectiveness of its use should also be taken into consideration. CLINICAL IMPLICATIONS: In the setting of catecholamine-resistant septic shock, our data shows that synthetic angiotensin II is associated with significant improvement in MAP at three hours compared to traditional third-line vasopressors and may play an important role in patients with catecholamine-resistant shock. DISCLOSURES: No relevant relationships by Maria Chaudhry, source=Web Response No relevant relationships by Murali Krishna, source=Web Response No relevant relationships by Karthika Linga, source=Web Response No relevant relationships by Isaac Pak, source=Web Response No relevant relationships by Lauren Stuczynski, source=Web Response

A case of catecholamine-resistant septic shock with polyuria after discontinuation of arginine vasopressin infusion

A case of catecholamine-resistant septic shock with polyuria after discontinuation of arginine vasopressin infusion

The therapeutic efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure: a single-center experience

BackgroundSepsis remains a common condition with high mortality when multiple organ failure develops. The evidence for therapeutic plasma exchange (TPE) in this setting is promising but inconclusive. Our study aims to evaluate the efficacy of adjunct TPE for septic shock with multiple organ failure compared to standard therapy alone.MethodsA retrospective, observational chart review was performed, evaluating outcomes of patients with catecholamine-resistant septic shock and multiple organ failure in intensive care units at a tertiary care hospital in Winston-Salem, NC, from August 2015 to March 2019. Adult patients with catecholamine-resistant septic shock (≥ 2 vasopressors) and evidence of multiple organ failure were included. Patients who received adjunct TPE were identified and compared to patients who received standard care alone. A propensity score using age, gender, chronic co-morbidities (HTN, DM, CKD, COPD), APACHE II score, SOFA score, lactate level, and number of vasopressors was used to match patients, resulting in 40 patients in each arm.ResultsThe mean baseline APACHE II and SOFA scores were 32.5 and 14.3 in TPE patients versus 32.7 and 13.8 in control patients, respectively. The 28-day mortality rate was 40% in the TPE group versus 65% in the standard care group (p = 0.043). Improvements in baseline SOFA scores at 48 h were greater in the TPE group compared to standard care alone (p = 0.001), and patients receiving adjunct TPE had a more favorable fluid balance at 48 h (p = 0.01). Patients receiving adjunct TPE had longer ICU and hospital lengths of stay (p = 0.003 and p = 0.006, respectively).ConclusionsOur retrospective, observational study in adult patients with septic shock and multiple organ failure demonstrated improved 28-day survival with adjunct TPE compared to standard care alone. Hemodynamics, organ dysfunction, and fluid balance all improved with adjunct TPE, while lengths of stay were increased in survivors. The study design does not allow for a generalized statement of support for TPE in all cases of sepsis with multiple organ failure but offers valuable information for a prospective, randomized clinical trial.

Vasopressin use in critically ill cirrhosis patients with catecholamine-resistant septic shock: The CVICU cohort.

AIMTo examine patient-centered outcomes with vasopressin (AVP) use in patients with cirrhosis with catecholamine-refractory septic shock.METHODSWe conducted a single center, retrospective cohort study enrolling adult patients with cirrhosis treated for catecholamine-resistant septic shock in the intensive care unit (ICU) from March 2011 through December 2013. Other etiologies of shock were excluded. Multivariable regression models were constructed for seven and 28-d mortality comparing AVP as a second-line therapy to a group of all other vasoactive agents.RESULTSForty-five consecutive patients with cirrhosis were treated for catecholamine-resistant septic shock; 21 received AVP while the remaining 24 received another agent [phenylephrine (10), dopamine (6), norepinephrine (4), dobutamine (2), milrinone (2)]. In general, no significant differences in baseline demographics, etiology of cirrhosis, laboratory values, vital signs or ICU mortality/severity of illness scores were observed with the exception of higher MELD scores in the AVP group (32.4, 95%CI: 28.6-36.2 vs 27.1, 95%CI: 23.6-30.6, P = 0.041). No statistically significant difference was observed in unadjusted 7-d (52.4% AVP vs 58.3% and P = 0.408) or 28-d mortality (81.0% AVP vs 87.5% non-AVP, P = 0.371). Corticosteroid administration was associated with lower 28-d mortality (HR = 0.37, 95%CI: 0.16-0.86, P = 0.021) independent of AVP use.CONCLUSIONAVP is similar in terms of patient centered outcomes of seven and 28-d mortality, in comparison to all other vasopressors when used as a second line vasoactive agent in catecholamine resistant septic shock. Large-scale prospective study would help to refine current consensus standards and provide further support to our findings.

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Background and aims: The role of corticosteroid therapy in septic shock is ill defined. Aims: To determine the impact of adjunctive corticosteroid therapy on the outcome of children with catecholamine resistant septic shock. Methods: Children (1 month – 18 years age) with catecholamine resistant septic shock were recruited during the study period between July 2012-December 2012. Children with low cortisol levels received hydrocortisone therapy as per septic shock guidelines. The outcome of these children were compared to the group with normal cortisol levels. Results: 60 out of 100 children with septic shock were catecholamine resistant. The proportion of children with low cortisol levels was 23/60 (38.3%). The demographic profile of the 2 goups were comparable in terms of median age in years (2(IQR 0.9,6) vs 3(IQR0.8,8)), gender ratio (M:F:: 0.8:1 vs 1:1) and median PRISM III Score [10(IQR 7,15) vs 15(IQR 8,20), p=0.17)]. Hydrocortisone therapy in the low cortisol level group improved survival as compared to the group with normal cortisol levels (52.2% vs 24.3%, p < 0.02). However, length of PICU stay [6 (IQR2,8) vs 4 (IQR 2,8)], hospital stay [8 (IQR 2,11.5) vs 4 (IQR 2,10)] in days, inotrope duration [84 (IQR 36,144) vs 72 (IQR 36,168)] and ventilation duration [84 (IQR 48,144) vs 72 (IQR 48,120)] in hours was not statistically significant (p>0.05). Conclusions: Our data strongly supports the use of hydrocortisone for catecholamine resistant septic shock. However, randomised control trials with larger sample size are warranted to define its role in the management of pediatric septic shock.

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Background and aims: The benefit from corticosteroids remains controversial in sepsis and septic shock and the presence of adrenal insufficiency (AI) has been proposed to justify steroid use. Aims: to determine adrenal state and its relation with outcome in critical children admitted with sepsis to PICU of Cairo University, Children Hospital. Methods: Thirty cases with sepsis and septic shock were studied. Cortisol levels (CL) were estimated at baseline and after high-dose short ACTH stimulation in those patients and in matched 30 controls. Absolute AI was defined as basal CL <7 micg/dl and peak CL <18 micg/dl. Relative AI was diagnosed if cortisol increment after stimulation is <9 microg/dL. Results: Overall mortality of cases was 50 %. The mean CL at baseline in cases was higher than that of controls (51.39 micg/dl vs 12.83 micg/dl, p=0.000). The mean CL 60 minutes after ACTH stimulation was higher than that of controls (73.38micg/dl vs 32.80 micg/dl, p=0.000). The median of % rise in cases was lower than that of controls (45.3 % vs 151.7%). There was positive correlation between basal and post-stimulation cortisol with number of system failure, inotropic support duration, mechanical ventilation days, and CO2 level in blood. There was negative correlation between basal and post stimulation cortisol with blood pH and HCO3. Conclusions: RAI is common with severe sepsis/septic shock. It is associated with more inotropic support and has higher mortality. Studies are warranted to determine whether corticosteroid therapy has a survival benefit in children with RAI and catecholamine resistant septic shock.

Adrenocortical status in infants and children with sepsis and septic shock

BackgroundThe benefit from corticosteroids remains controversial in sepsis and septic shock and the presence of adrenal insufficiency (AI) has been proposed to justify steroid use. AimTo determine adrenal state and its relation with outcome in critical children admitted with sepsis to PICU of Cairo University, Children Hospital. MethodsThirty cases with sepsis and septic shock were studied. Cortisol levels (CL) were estimated at baseline and after high-dose short ACTH stimulation in those patients and in 30 matched controls. Absolute AI was defined as basal CL<7μg/dl and peak CL<18μg/dl. Relative AI was diagnosed if cortisol increment after stimulation is <9μg/dl. ResultsOverall mortality of cases was 50%. The mean CL at baseline in cases was higher than that of controls (51.39μg/dl vs. 12.83μg/dl, p=0.000). The mean CL 60min after ACTH stimulation was higher than that of controls (73.38μg/dl vs. 32.80μg/dl, p=0.000). The median of %rise in cases was lower than that of controls (45.3% vs. 151.7%). There was a positive correlation between basal and post-stimulation cortisol with number of system failure, inotropic support duration, mechanical ventilation days, and CO2 level in blood. There was a negative correlation between basal and post stimulation cortisol with blood pH and HCO3. ConclusionRAI is common with severe sepsis/septic shock. It is associated with more inotropic support and has higher mortality. Studies are warranted to determine whether corticosteroid therapy has a survival benefit in children with RAI and catecholamine resistant septic shock.

Arterial bicarbonate may be a useful indicator of inadequate cortisol response in children with catecholamine resistant septic shock

To study the clinical and biochemical parameters that can predict cortisol insufficiency in children with septic shock. prospective, observational study. Tertiary health-care center. Fifty children admitted with the catecholamine resistant septic shock to a tertiary health-care center. At the time of hospitalization all patients underwent detailed clinical evaluation including, history and physical examination, evaluation with the complete blood count, serum cortisol, renal function tests, liver function tests, prothrombin time activated partial thromboplastin time, arterial blood gas analysis, urine analysis, chest roentgenogram, ultrasonography of the abdomen and chest, urine, and blood culture for bacteria and fungi. Out of 50 children with the catecholamine resistant septic shock, seven had adrenal insufficiency (serum cortisol <18 μg/dl). Of all parameters studied, only arterial bicarbonate at the time of admission to intensive care predicted adrenal insufficiency. On Receptor operative characteristic curve analysis, a bicarbonate level of 10.9 mEq/L had the best accuracy to predict adrenal insufficiency. Arterial bicarbonate may be used as a rapid test for provisional identification of adrenal insufficiency among children with the catecholamine resistant septic shock.

Vasopressin and Terlipressin in Neonates and Children with Refractory Septic Shock

Vasopressin and its analogue terlipressin are potent vasopressors which have been recently proposed in the treatment of catecholamine-resistant septic shock. We review the physiology, metabolism and pharmacology of vasopressin and terlipressin, as well as the available data on their efficacy and safety in neonates and children with septic shock. In adults, vasopressin deficiency can contribute to refractory shock states associated with sepsis. Differently, in children with septic shock vasopressin levels may be normal or even augmented. Nevertheless, low doses of vasopressin and terlipressin seem to have the potential to restore vasomotor tone in conditions refractory to catecholamines, improving organ perfusion with preservation of renal blood flow, while decreasing catecholamine requirements. Vasopressin and terlipressin produce vasoconstriction via stimulation of V1-receptors. In particular, terlipressin has a higher selectivity for V1-receptors and a longer half-life when compared to vasopressin, allowing for intermittent bolus doses. However, the pharmacology of vasopressin/terlipressin in newborns and children has not been sufficiently investigated and data on potential short and long-term adverse effects are still lacking. Further clinical, pharmacokinetic and pharmacodynamic studies are needed to better define the role of vasopressin and terlipressin in septic shock, as well as to prove their effectiveness and safety in infants and children.

Terlipressin in the treatment of late phase catecholamine-resistant septic shock.

Norepinephrine, but also dopamine and epinephrine are recommended as first line vasopressors in the treatment of septic shock. In some patients, septic shock deteriorates and becomes to be resistant to catecholamines. In this situation, addition of vasopressin or terlipressin can be advantageous. The aim of our pilot study was to evaluate the impact of terlipressin on open label norepinephrine requirements and mortality. In a randomized, controlled, single centre study we assigned patients with late advanced septic shock refractory to catecholamines (norepinephrine >0.6µg/kg/min for more than 24h) to receive either continuously terlipressin 4mg/24h for 72 hours in addition to open label norepinephrine (TERLI group) or to continue therapy only with catecholamines (CON group). All vasopressor infusions were titrated to maintain a target blood pressure. We enrolled 30 patients, of whom 13 were assigned to terlipressin and in 17 we continued in catecholamine therapy. There was no significant difference in norepinephrine consumption between the groups. Open label norepinephrine infusion rates decreased significantly in the TERLI group as compared with initial consumption, but the decrease we observed only in 7 (54%) patients. There was no significant difference between groups in the rate of death at day 28 (77% in TERLI group and 94% in CON group; p=0.18) or at day 90 (91% vs. 94%; p=0.85). Continuous terlipressin infusion was not effective in reducing norepinephrine consumption or in the mortality of patients, if administered in late phase of catecholamine refractory septic shock.

Continuous Terlipressin Infusion as Rescue Treatment in a Case Series of Children with Refractory Septic Shock

Despite intensive therapy, refractory pediatric septic shock has a high rate of morbidity and mortality. Additional treatments are needed to improve outcomes in such cases. To report the clinical effects of continuous terlipressin infusion as rescue treatment for children with septic shock refractory to high catecholamine doses. Sixteen episodes of catecholamine-resistant septic shock were recorded in 15 children (aged from newborn to 15 years) who received compassionate rescue treatment with terlipressin at 6 pediatric intensive care units. Terlipressin treatment consisted of a loading dose (20 μg/kg) followed by continuous infusion at a rate of 4-20 μg/kg/h. Terlipressin was titrated at increases of 1 μg/kg/h to maintain mean arterial pressure (MAP) in normal range for age and to reduce catecholamine dosage. The main outcome was survival of the episode. Secondary outcomes included hemodynamic effects, ischemia, and terlipressin-related adverse events. Terlipressin increased median MAP from 48 (range 42-63) to 68 (45-115) mm Hg 30 minutes after terlipressin administration (p < 0.01). MAP was subsequently sustained, which allowed for the reduction of norepinephrine infusion from 2 μg/kg/min (1-4) at baseline to 1.5 μg/kg/min (0.4-4) at 1 hour, 1.3 μg/kg/min (0-8) at 4 hours, 1 μg/kg/min (0-2) at 12 hours, 0.45 μg/kg/min (0-1.4) at 24 hours, and 0 μg/kg/min (0-0.6) at 48 hours (p < 0.05 vs baseline in all cases). In 8 (50%) of the 16 septic shock episodes the patients survived, 7 (44%) without sequelae. One patient survived with sequelae (minor amputation and mild cutaneous ischemia). Eight patients had signs of ischemia at admission; terlipressin induced reversible ischemia in another 4 patients. Meningococcal infection, prior ischemia, and MAP were risk factors for mortality. Continuous terlipressin infusion may improve hemodynamics and survival in some children with refractory septic shock. Terlipressin could contribute to tissue ischemia.

GLUCOCORTICOID TREATMENT-EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal regulation of epinephrine synthesis during stress.

The long-term survival rate of catecholamine-resistant septic shock in Japanese patients who received vasopressin therapy

Septic shock is associated with vasopressin deficiency and hypersensitivity to its exogenous administration. The aim of this study is to review the 28-day survival rate, hemodynamic and renal effects of vasopressin therapy in refractory septic shock Japanese patients. 55 Japanese patients experiencing catecholamine-resistant septic shock were treated with vasopressin. Hemodynamic alterations and the serum concentrations of aspartate aminotransferase, total bilirubin and creatinine clearance were evaluated following vasopressin treatment. In both, survivors and non-surviving patients, treatment with vasopressin resulted in a significantly increase in mean arterial pressure, hourly urine output, and a significant decrease in heart rate and total pressor dosage requirements. Creatinine clearance was significantly increased only in survivors. There were no significant changes in the serum concentrations of aspartate aminotransferase and total bilirubin. The 28-day survival rate was 45% (25 patients). In Japanese septic shock patients, vasopressin infusion improved hemodynamic status and reduced catecholamine requirement, and 28-day survival rate was 45%.

Arginine vasopressin increases plasma levels of von Willebrand factor in sheep

The V1a/V2 receptor dual-agonist arginine vasopressin (AVP) is increasingly used in catecholamine-resistant septic shock [1]. While V1a receptor stimulation results in vasoconstriction, V2 receptor stimulation promotes coagulation, at least in part through an increase in plasma von Willebrand factor antigen (vWF:Ag) activity. We hypothesized that, at an intravenous infusion rate representative of the requirements for the treatment of sepsis-induced vasodilatory hypotension in sheep [2], AVP provides procoagulant activities. We tested this hypothesis by measuring vWF:Ag activity in unanesthetized healthy sheep during administration of AVP in comparison with the vWF:Ag activity increase induced by the selective V2 receptor agonist desmo-pressin (dDAVP).

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.

Recently published papers: Sepsis – guidelines, treatment and novel approaches

The choice of inotropic agent, particularly in catecholamine-resistant septic shock, remains an area of debate. Here we discuss a recent trial examining the use of vasopressin in a carefully controlled trial setting. Yet more data on the use of drotrecogin alfa (activated) in septic shock are described, as are novel but as yet experimental approaches to the treatment of sepsis. Finally, it is important not to forget to read the latest surviving sepsis guidelines.

Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children

To evaluate the effect of terlipressin on oxygenation, PaO2/FIO2, heart rate, mean arterial pressure, and mortality in children with septic shock refractory to high doses of dopamine/dobutamine and adrenaline. A randomized, nonblind study in the pediatric intensive care unit of a university hospital. We studied 58 children with septic shock and refractory hypotension despite fluid loading and high doses of catecholamines, randomly enrolled to terlipressin (TP, n=30) or control (n=28). TP was administered as intravenous bolus doses of 20 microg/kg every 6 h for a maximum of 96 h. Hemodynamic changes, PaO2/FIO2 rates, length of stay, and mortality rate in PICU were recorded prospectively. Mean arterial pressure and PaO2/FIO2 significantly increased, and heart rate significantly decreased 30 min after each TP treatment, but mortality did not differ from control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group (13.4+/-7.9 vs. 20.2+/-9.7 days and was longer among nonsurvivors of the TP group vs. control (10.4+/-6.9 vs. 6.2+/-3.4 days). Blood urea nitrogen, creatinine, AST, ALT, and urine output of patients in the TP group did not change after terlipressin. Although terlipressin infusion had no effect on mortality, it significantly increases mean arterial pressure, PaO2/FIO2, and survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but warrants further evaluation as a rescue therapy in refractory septic shock.

CONTINUOUS VERSUS BOLUS INFUSION OF TERLIPRESSIN IN OVINE ENDOTOXEMIA

In patients with sepsis, hemodynamic support is often complicated by a tachyphylaxis against conventional vasopressor agents. Bolus infusion of terlipressin, a vasopressin analog, has been reported to increase mean arterial pressure in patients with catecholamine-resistant septic shock. However, bolus infusion of terlipressin may be associated with severe side effects, including pulmonary vasoconstriction and impairment of oxygen delivery. We hypothesized that continuous low-dose infusion of terlipressin may reverse sepsis-related systemic arterial hypotension with reduced side effects as compared with the traditional concept of bolus administration. Twenty-seven adult sheep were instrumented for chronic study. After a baseline measurement, Salmonella typhosa endotoxin (10 ng.kg-1.min-1) was continuously administered for the next 40 h. After 16 h of endotoxemia, the surviving sheep (n = 24) were randomly assigned to be treated with either a continuous infusion of terlipressin (2 mg for 24 h), bolus injections of terlipressin (1 mg every 6 h), or placebo (normal saline; each n = 8). Continuous infusion of terlipressin permanently reversed endotoxin-induced systemic arterial hypotension (P < 0.001) and improved left ventricular stroke work index in all sheep (P < 0.05). Intermittent bolus injections of terlipressin were linked to decreases in heart rate and cardiac index and increases in pulmonary vascular resistance index (each, P < 0.001). These unwanted side effects were prevented by continuous low-dose infusion of the drug. In conclusion, continuous infusion of terlipressin stabilized hemodynamics and improved myocardial performance in endotoxemic ewes without obvious side effects. Continuous low-dose terlipressin infusion may represent a useful alternative treatment of arterial hypotension related to sepsis and systemic inflammatory response syndrome.

Vasopressin in septic shock: effects on pancreatic, renal, and hepatic blood flow

IntroductionVasopressin has been shown to increase blood pressure in catecholamine-resistant septic shock. The aim of this study was to measure the effects of low-dose vasopressin on regional (hepato-splanchnic and renal) and microcirculatory (liver, pancreas, and kidney) blood flow in septic shock.MethodsThirty-two pigs were anesthetized, mechanically ventilated, and randomly assigned to one of four groups (n = 8 in each). Group S (sepsis) and group SV (sepsis/vasopressin) were exposed to fecal peritonitis. Group C and group V were non-septic controls. After 240 minutes, both septic groups were resuscitated with intravenous fluids. After 300 minutes, groups V and SV received intravenous vasopressin 0.06 IU/kg per hour. Regional blood flow was measured in the hepatic and renal arteries, the portal vein, and the celiac trunk by means of ultrasonic transit time flowmetry. Microcirculatory blood flow was measured in the liver, kidney, and pancreas by means of laser Doppler flowmetry.ResultsIn septic shock, vasopressin markedly decreased blood flow in the portal vein, by 58% after 1 hour and by 45% after 3 hours (p < 0.01), whereas flow remained virtually unchanged in the hepatic artery and increased in the celiac trunk. Microcirculatory blood flow decreased in the pancreas by 45% (p < 0.01) and in the kidney by 16% (p < 0.01) but remained unchanged in the liver.ConclusionVasopressin caused marked redistribution of splanchnic regional and microcirculatory blood flow, including a significant decrease in portal, pancreatic, and renal blood flows, whereas hepatic artery flow remained virtually unchanged. This study also showed that increased urine output does not necessarily reflect increased renal blood flow.

Vasopressin in catecholamine‐resistant septic and cardiogenic shock in very‐low‐birthweight infants

To evaluate vasopressin as a rescue therapy in catecholamine-refractory septic and cardiogenic shock in very-low-birthweight (VLBW) infants. Prospective assessment of vasopressin therapy in three VLBW infants with catecholamine-refractory septic shock (24 + 6 wk, 600 g) and cardiogenic shock (26 + 1 wk, 890 g; 26 + 1 wk, 880 g) at a university hospital. Adequate systemic arterial blood pressure could only be restored after vasopressin administration as a continuous infusion over a 36-h period in the preterm suffering from septic shock; in the two neonates with cardiogenic shock, only a transient stabilization in mean arterial pressure was observed, which did not impact on the poor prognosis. Although vasopressin appears to be a suitable rescue therapy in catecholamine-resistant septic shock in VLBW infants, further evaluation in controlled clinical trials is warranted.