To determine the patterns of oxygen consumption (Vo2) using indirect calorimetry (IC) for the first 24 hrs after serious blunt traumatic injury.
Prospective, observational study.
Surgical intensive ...care unit of a Level 1 trauma center.
Sixty-six mechanically ventilated patients with blunt traumatic injury and Injury Severity Score >15.
IC for 24 hrs postinjury. Patients were resuscitated to standard parameters of perfusion.
Mean patient age was 50.1+/-18.7 yrs with a mean Injury Severity Score 30.7+/-11.3). Mean Vo2 for all patients for the 24-hr study period was 168.5+/-29.5 mL/min/m2. The level of Vo2 was not related to Injury Severity Score, the number or combination of organ systems injured, or to the use of vasoactive agents. Patients >65 yrs of age had significantly lower Vo2 (P = .0038) compared with patients < or =50 yrs. Vo2 did not change over time after resuscitation to normal parameters of perfusion. Mean Vo2 was 156.5+/-63.2 mL/min/m2 in patients who developed multiple organ dysfunction, and 172.4+/-33.3 mL/min/m2 in those who did not develop multiple organ dysfunction (p = .16).
Seriously injured patients are hypermetabolic in the early postinjury period. The level of Vo2 is unrelated to injury severity or number of organ systems involved. Elderly patients can be expected to have lower levels of Vo2. Vo2 does not change significantly in response to resuscitation to normal parameters of perfusion. Vo2 measured by IC did not predict the development of multiple organ dysfunction.
Critically ill patients usually have multiple risk factors for the development of pressure ulcers. Pressure ulcers involve all levels of tissue from bone to skin, and result from excessive pressure ...and shearing. Control of incontinence, maintenance of adequate oxygen delivery and nutritional support is the key to minimizing the effects of skin breakdown in the intensive care unit. Consistent assessment and surveillance of skin for early signs of pressure ulcer development are essential, as is an interdisciplinary approach with nursing specialists and surgical consultants for pressure ulcers that have developed.
Concerns exist about the effect of flexible fiberoptic bronchoscopy (FFB) on intracranial pressure (ICP). We studied the effect of FFB on cerebral hemodynamics in patients with severe head injury.
...Prior to FFB, patients were anesthetized and muscle relaxants were given as necessary to eliminate coughing. Comparisons were made of mean arterial pressure (MAP), ICP, and cerebral perfusion pressure (CPP) prior to, during, and after FFB, as well as comparisons of mean cerebral hemodynamic values in an 8-hour period before and after FFB. Observations were made of changes in neurologic status post-FFB.
Surgical intensive care unit of Level 1 Trauma Center.
Fifteen patients with severe head injury in whom ICP was monitored and who required FFB for diagnosis of nosocomial pneumonia or treatment of lobar collapse.
Pre-FFB ICP averaged 14.3 mm Hg (range, 6 to 26 mm Hg). During FFB, patients experienced a mean increase in ICP of 13.5 mm Hg above basal values (p=0.0001). At peak ICP, MAP increased from a baseline of 92.3 mm Hg (SD±16.1) to 111.5 mm Hg (±13.9). Mean CPP was 83.7 mm Hg at peak ICP (range, 52 to 121 mm Hg), a 14.0% increase over baseline. The ICP and MAP returned to basal levels following bronchoscopy. No patient had a clinically significant increase in ICP or demonstrated any deterioration in Glasgow Coma Scale score or neurologic examination findings post-FFB.
Although FFB causes an increase in ICP in patients with severe head injury, MAP also rises, and an adequate CPP is maintained. The ICP returns to basal levels after the procedure. When properly performed, FFB does not adversely affect neurologic status in patients with severe head injury.
The purpose of this study was to compare the measurements of whole body oxygen consumption determined by the Fick method and by indirect calorimetry in mechanically ventilated patients with multiple ...trauma.
A prospective, correlational, within-subjects design.
Surgical intensive care unit of a Level I trauma center.
Thirty-eight mechanically ventilated adults with multiple injuries who received a pulmonary artery catheter within 24 hrs of admission to the surgical intensive care unit.
After the initial resuscitation, simultaneous measurements of oxygen consumption (V(O2) by the reverse Fick equation and by indirect calorimetry were performed every 6 hrs for 24 hrs in normothermic patients who were at rest for at least 30 mins. At each measurement period, the mean V(O2) values determined by indirect calorimetry were significantly greater than the mean V(O2) values determined by the Fick method (time 1: 172+/-38 vs. 125+/-47 mL/min/m2, p < .0001; time 2: 170+/-31 vs. 130+/-48 mL/min/m2, p < .0001; time 3: 170+/-32 vs. 132+/-53 mL/min/m2, p < .0001; time 4: 169+/-29 vs. 130+/-60 mL/min/m2, p < .0002). By using the Bland and Altman technique, the mean bias was 41+/-3.95 mL/min/m2. Correlation coefficients of VO2 values between methods of measurements were statistically significant (r2 = .32, p = .0001; r2 = .32, p = .0001; r2 = .33, p = .0001; r2 = .18, p = .0001).
Indirect calorimetry should be the preferred standard for measurement of oxygen consumption in severely injured patients.
Tigloyl-CoA:pseudotropine acyl transferase esterifies the 3β-hydroxyl group of pseudotropine (3β-hydroxytropane) with the tiglic acid moiety of tigloyl-Coenzyme A. This enzyme was purified to near ...electrophoretic homogeneity—about 330-fold—from transformed root cultures of
Datura stramonium. The protocol involved the sequential use of ammonium sulphate precipitation, hydrophobic interaction, anion-exchange, chromatofocusing and gel filtration chromatography. The enzyme has a
M
r
of 65 000, as determined by gel filtration chromatography on Sepharose 6 and SDS-PAGE electrophoresis, indicating it to be active as a monomer. Maximal activity occurs at pH 9.0 but the enzyme is still about 30% active at pH 7.0. The purified protein shows simple Michaelis-Menten kinetic behaviour, with
K
m values of 0.36 and 1.31 mM for pseudotropine and tigloyl-CoA, respectively. The enzyme is specific for the acyl group receptor. Of a range of potential acceptors tested, only pseudotropine and 4-hydroxy-1-methylpiperidine (14%) were used: tropine (3α-hydroxytropane) and norpseudotropine were not acylated. In contrast, the enzyme possesses the ability to transfer the acyl moiety to pseudotropine from a wide range of aliphatic acyl-CoA thioesters. Tigloyl-CoA and acetyl-CoA act recuprocally as competitive inhibitors, suggesting that they compete for the same active site on the enzyme. With acetyl-CoA the
K
m is 0.33 mM, indicating that the enzyme has a higher affinity for this acyl donor than for tigloyl-CoA. Neither CoA nor any of the alkamine acceptors tested were able to inhibit the acylation of pseudotropine.
The nortropane sulphur analogues 8-thiabicyclo3.2.1octan-3-one, 8-thiabicyclo3.2.1octan-3α-ol and 8-thiabicyclo3.2.1octan-3β-ol have been found to have differential effects in vitro on the activities ...of tropinone reductase I and tropinone reductase II from Datura stramonium L. It has been demonstrated that only tropinone reductase I is able to metabolise 8-thiabicyclo3.2.1octan-3-one and that only this enzyme is inhibited by 8-thiabicyclo3.2.1octan-3α-ol and 8-thiabicyclo3.2.1octan-3β-ol. A Km of 0.035 mM was determined for 8-thiabicyclo3.2.1octan-3-one and I50 values of 0.081 mM and 0.021 mM for 8-thiabicyclo3.2.1octan-3α-ol and 8-thiabicyclo3.2.1octan-3β-ol, respectively. The influence that these differential interactions might have on metabolism was investigated in transformed root cultures of D. stramonium. It was found that when these cultures were grown in the presence of either 8-thiabicyclo3.2.1octan-3-one or 8-thiabicyclo3.2.1octan-3β-ol the spectrum of alkaloids that accumulated was altered from that found in control roots in the manner predicted from the observed effects of these inhibitors on the isolated reductases. The effect could be mimicked by feeding pseudotropine, the product of tropinone reductase II. It is concluded that the relative levels of activity of the two tropinone reductases might play an important role in regulating the balance of tropan-3α-ols to tropan-3β-ols seen in the spectrum of tropane-alkaloid-producing plants.
Putrescine-N-methyltransferase (PMT; EC 2.1.1.53), the first enzyme in the biosynthetic pathway leading from putrescine to tropane and pyrrolidine alkaloids, has been purified about 700-fold from ...root cultures of Datura stramonium established following genetic transformation with Agrabacterium rhizogenes. The native enzyme had a molecular weight estimated by gel-permeation chromatography on Superose-6 of 40 kDa; sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the peak fractions from Superose-6 chromatography revealed a band of 36 kDa molecular weight. Kinetic studies of the purified enzyme gave Km values for putrescine and S-adenosyl-L-methionine of 0.31 mM and 0.10 mM, respectively, and Ki values for S-adenosyl-L-homocysteine and N-methylputrescine of 0.01 mM and 0.15 mM, respectively. The enzyme was active with some derivatives and analogous of putrescine, including 1,4-diamino-2-hydroxybutane and 1,4-diamino-trans-but-2-ene. Little activity was observed with 1,4-diamino-cis-but-2-ene and none with 1,3-diaminopropane or 1,5-diaminopentane (cadaverine), indicating a requirement for substrate activity of two amino groups in a trans conformation, separated by four carbon atoms. A large number of monoamines were inhibitors of the enzyme. Though not a substrate, cadaverine was a competitive inhibitor of the enzyme, with a Ki of 0.04 mM; the significance of this in relation to the biosynthesis of cadaverine-derived alkaloids is discussed.
The purpose of this study was to evaluate the relation of oxygen delivery (DO2) to the occurrence of multiple organ dysfunction (MOD) in patients with ruptured abdominal aortic aneurysms (AAA).
...Patients with ruptured AAA are at high risk for the development of MOD and death. Previous reports of high-risk general surgical patients have shown improved survival when higher levels of DO2 are achieved.
Hemodynamic data were collected at 4-hour intervals on 57 consecutive patients (mean age, 70.5 years) who survived 24 hours after repair of infrarenal ruptured AAA. Patients were resuscitated to standard parameters of perfusion (pulse, blood pressure, urine output, normal base deficit). MOD was determined based on six organ systems. Standard parametric (analysis of variance, t tests) and nonparametric (chi square, Wilcoxon) tests were used to compare hemodynamic data, red blood cell requirements, colon ischemia, and organ failure for patients with and without MOD.
Patients who developed MOD had a significantly lower cardiac index and DO2 for the first 12 hours; the difference was most significant at 8 hours. Logistic regression analysis demonstrated that the strongest predictors of MOD were DO2, early onset of renal failure, and total number of red blood cells transfused.
DO2 is an earlier and better predictor of MOD after ruptured AAA than previously identified risk factors. Failure to achieve a normal DO2 in the first 8 hours after repair is strongly associated with the development of MOD and a high mortality. Strategies to restore normal DO2 may be useful to improve outcome in these high-risk patients.
Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. ...Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments.
Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC-MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests.
Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines.
Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.
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