Neuroinflammation often develops in sepsis along with increasing permeability of the blood-brain barrier (BBB), which leads to septic encephalopathy. The barrier is formed by tight junction ...structures between the cerebral endothelial cells. We investigated the expression of tight junction proteins related to endothelial permeability in brain autopsy specimens in critically ill patients deceased with sepsis and analyzed the relationship of BBB damage with measures of systemic inflammation and systemic organ dysfunction.
The case series included all (385) adult patients deceased due to sepsis in the years 2007-2015 with available brain specimens taken at autopsy. Specimens were categorized according to anatomical location (cerebrum, cerebellum). The immunohistochemical stainings were performed for occludin, ZO-1, and claudin. Patients were categorized as having BBB damage if there was no expression of occludin in the endothelium of cerebral microvessels.
Brain tissue samples were available in 47 autopsies, of which 38% (18/47) had no expression of occludin in the endothelium of cerebral microvessels, 34% (16/47) developed multiple organ failure before death, and 74.5% (35/47) had septic shock. The deceased with BBB damage had higher maximum SOFA scores (16 vs. 14, p = 0.04) and more often had procalcitonin levels above 10 μg/L (56% vs. 28%, p = 0.045) during their ICU stay. BBB damage in the cerebellum was more common in cases with C-reactive protein (CRP) above 100 mg/L as compared with CRP less than 100 (69% vs. 25%, p = 0.025).
In fatal sepsis, damaged BBB defined as a loss of cerebral endothelial expression of occludin is related with severe organ dysfunction and systemic inflammation.
Introduction
Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our ...knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients.
Materials and methods
In this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone’s effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS).
Results
All patients received additional levobupivacaine doses on parturients’ requests. The first dose was requested at a median of 163 min (range 19–303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone’s distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation.
Conclusions
The optimal dose of hydromorphone in labour pain warrants further evaluation.
To determine whether changes in transcranial near‐infrared spectroscopy (NIRS) values reflect changes in cardiac index (CI) in adult cardiac surgical patients. Single‐center prospective post hoc ...analysis. University hospital. One hundred and twenty‐four adult patients undergoing cardiac surgery. In each patient, several CI measurements were taken, and NIRS values were collected simultaneously. We used a hierarchical linear regression model to assess the association between NIRS values and CI. We calculated a crude model with NIRS as the only factor included, and an adjusted model, where mean arterial pressure, end‐tidal CO2, and oxygen saturation were used as confounding factors. A total of 1301 pairs of NIRS and CI values were collected. The analysis of separate NIRS and CI pairs revealed a poor association, which was not statistically significant when adjusted with the chosen confounders. However, when the changes in NIRS from baseline or from the previous measurement were compared to those of CI, a clinically and statistically significant association between NIRS and CI was observed also in the adjusted model. Compared to the baseline and to the previous measurement, respectively, the regression coefficients with 95% confidence intervals were 0.048 (0.041–0.056) and 0.064 (0.055–0.073) in off‐pump coronary artery bypass patients and 0.022 (0.016–0.029) and 0.026 (0.020–0.033) in patients who underwent cardiopulmonary bypass. In an unselected cardiac surgical population, the changes in NIRS values reflect those in CI, especially in off‐pump coronary artery bypass patients. In this single‐center post hoc analysis of data from a prospectively collected database of cardiac surgery patients, paired measurements of cardiac output and NIRS revealed that while there was a no correlation between individual paired measurements, a small correlation was found in changes in the two measurements from baseline values. This highlights a potential to utilize changes in NIRS from baseline to suggest changes in cardiac output in cardiac surgical populations.
To determine whether central venous oxygen saturation (ScvO2) measurements could be used interchangeably with mixed venous oxygen saturation (SvO2) measurements in adult cardiac surgery patients.
A ...single-center prospective observational study.
A university hospital.
Eighty-five adult patients undergoing cardiac surgery.
The study authors compared the oxygen saturations in 590 pairs of venous blood samples drawn from the pulmonary artery catheter (PAC) at three different time points during surgery and four different time points in the intensive care unit. They compared samples obtained from the distal pulmonary artery line (SvO2) to those drawn from the proximal central venous line of the PAC (ScvO2) with the Bland-Altman test and the four-quadrant method.
The mean bias between SvO2 and ScvO2 was –1.9 (95% confidence interval CI, –2.3 to –1.5) and the limits of agreement (LOA) were –11.5 to 7.6 (95% CI, –12.5 to –10.7 and 6.8-8.5, respectively). The percentage error (PE) was 13.2%. Based on the four-quadrant plot, only 50% of the measurement pairs were in agreement, indicating deficient trending ability.
ScvO2 values showed acceptable accuracy as the mean bias was low. The precision was inadequate; although the PE was acceptable, the LOA were wide. Trending ability was inadequate. The authors cannot recommend the use of ScvO2 values interchangeably with SvO2 measurements in the management of adult cardiac surgery patients.
Background
Surgical treatment of ankle fracture is associated with significant pain and high postoperative opioid consumption. The anaesthesia method may affect early postoperative pain. The main ...objective of the study was to compare postoperative opioid consumption after ankle‐fracture surgery between patients treated with spinal anaesthesia and general anaesthesia.
Methods
We reviewed retrospectively the files of 586 adult patients with surgically treated ankle fracture in the years 2014 through 2016. The primary outcome was opioid consumption during the first 48 postoperative hours. Secondary outcomes were maximal pain scores, postoperative nausea and vomiting, the length of stay in the post‐anaesthesia care unit, and opioid use in different time periods up to 48 h postoperatively. Propensity score matching was used to mitigate confounding variables.
Results
Total opioid consumption 48 h postoperatively was significantly lower after spinal anaesthesia (propensity score‐matched population: effect size −13.7 milligrams; 95% CI −18.8 to −8.5; P < .001). The highest pain score on the numerical rating scale in the post‐anaesthesia care unit was significantly higher after general anaesthesia (propensity score‐matched population: effect size 3.7 points; 95% CI 3.2‐4.2; P < .001). A total of 60 patients had postoperative nausea and vomiting in the post‐anaesthesia care unit, 53 (88.3%) of whom had general anaesthesia (P = .001).
Conclusions
Patients with surgically treated ankle fracture whose operation was performed under general anaesthesia used significantly more opioids in the first 48 h postoperatively, predominantly in the post‐anaesthesia care unit, compared with patients given spinal anaesthesia.
Purpose
Adequate nutrition after major abdominal surgery is associated with less postoperative complications and shorter hospital length of stay (LOS) after elective procedures, but there is a lack ...of studies focusing on the adequacy of nutrition after emergency laparotomies (EL). The aim of the present study was to investigate nutrition adequacy after EL in surgical ward.
Methods
The data from 405 adult patients who had undergone emergency laparotomy in Oulu University Hospital (OUH) between years 2015 and 2017 were analyzed retrospectively. Nutrition delivery and complications during first 10 days after the operation were evaluated.
Results
There was a total of 218 (53.8%) patients who were able to reach cumulative 80% nutrition adequacy during the first 10 postoperative days. Patients with adequate nutrition (> 80% of calculated calories) met the nutritional goals by the second postoperative day, whereas patients with low nutrition delivery (< 80% of calculated calories) increased their caloric intake during the first 5 postoperative days without reaching the 80% level. In multivariate analysis, postoperative ileus 4.31 (2.15–8.62),
P
< 0.001, loss of appetite 3.59 (2.18–5.93),
P
< 0.001 and higher individual energy demand 1.004 (1.003–1.006),
P
= 0.001 were associated with not reaching the 80% nutrition adequacy.
Conclusions
Inadequate nutrition delivery is common during the immediate postoperative period after EL. Oral nutrition is the most efficient way to commence nutrition in this patient group in surgical ward. Nutritional support should be closely monitored for those patients unable to eat.
Trial registration number
Not applicable.
Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate ...the effect and tolerability of blood-brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood-brain barrier disruption treatment was initiated 3-4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood-brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood-brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile.
A pneumatic tourniquet is often used during ankle fracture surgery to reduce bleeding and enhance the visibility of the surgical field. Tourniquet use causes both mechanical and ischemic pain. The ...main purpose of this study was to evaluate the effect of tourniquet time on postoperative opioid consumption after ankle fracture surgery.
We retrospectively reviewed the files of 586 adult patients with surgically treated ankle fractures during the years 2014-2016. We evaluated post hoc the effect of tourniquet time on postoperative opioid consumption during the first 24 h after surgery. The patients were divided into quartiles by the tourniquet time (4-43 min; 44-58 min; 59-82 min; and ≥83 min). Multivariable linear regression analysis was used to evaluate the results.
Tourniquets were used in 486 patients. The use of a tourniquet was associated with an increase in the total postoperative opioid consumption by 5.1 mg (95 % CI 1.6-8.5; p=0.004) during the first 24 postoperative hours. The tourniquet time over 83 min was associated with an increase in the mean postoperative oxycodone consumption by 5.4 mg (95 % CI 1.2 to 9.7; p=0.012) compared to patients with tourniquet time of 4-43 min.
The use of a tourniquet and prolonged tourniquet time were associated with higher postoperative opioid consumption during the 24 h postoperative follow-up after surgical ankle fracture fixation. The need for ethical approval and informed consent was waived by the Institutional Review Board of Northern Ostrobothnia Health District because of the retrospective nature of the study.
Various malignancies with peritoneal carcinomatosis are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The hemodynamic instability resulting from fluid ...balance alterations during the procedure necessitates reliable hemodynamic monitoring. The aim of the study was to compare the accuracy, precision and trending ability of two less invasive hemodynamic monitors, bioreactance-based Starling SV and pulse power device LiDCOrapid with bolus thermodilution technique with pulmonary artery catheter in the setting of cytoreductive surgery with HIPEC.
Thirty-one patients scheduled for cytoreductive surgery were recruited. Twenty-three of them proceeded to HIPEC and were included to the study. Altogether 439 and 430 intraoperative bolus thermodilution injections were compared to simultaneous cardiac index readings obtained with Starling SV and LiDCOrapid, respectively. Bland-Altman method, four-quadrant plots and error grids were used to assess the agreement of the devices.
Comparing Starling SV with bolus thermodilution, the bias was acceptable (0.13 l min
m
, 95% CI 0.05 to 0.20), but the limits of agreement were wide (- 1.55 to 1.71 l min
m
) and the percentage error was high (60.0%). Comparing LiDCOrapid with bolus thermodilution, the bias was acceptable (- 0.26 l min
m
, 95% CI - 0.34 to - 0.18), but the limits of agreement were wide (- 1.99 to 1.39 l min
m
) and the percentage error was high (57.1%). Trending ability was inadequate with both devices.
Starling SV and LiDCOrapid were not interchangeable with bolus thermodilution technique limiting their usefulness in the setting of cytoreductive surgery with HIPEC.
In this investigation, we studied the expression of inducible nitric oxide synthase (iNOS) and its association to apoptosis and angiogenesis in 43 in situ and 68 invasive breast carcinomas. Its ...expression was studied immunohistochemically using a polyclonal iNOS antibody, and the staining was evaluated both in tumor and stromal cells. Apoptosis was detected by 3' end labeling of fragmented DNA (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Vascularization was detected immunohistochemically using an antibody to the FVIII-related antigen, and calculated microvessel densities were determined. In addition to strong iNOS expression in stromal cells, iNOS positivity was observed in tumor cells in 46.5% of in situ and 58.8% of invasive carcinomas. In invasive carcinomas, there were more cases with iNOS positivity both in tumor and stromal cells compared to in situ carcinomas (0.007). The proportion of cases with iNOS-positive tumor cells increased in in situ carcinomas from grade I to III (20.0%, 46.2%, and 73.3%). In invasive ductal carcinomas, there were more cases with iNOS-positive tumor cells than with in situ carcinomas (P = 0.04). Carcinomas with both iNOS-positive tumor and stromal cells had a higher apoptotic index (P = 0.02) and a higher calculated microvessel densities index (P = 0.02). A high number of iNOS-positive stromal cells associated with metastatic disease (P = 0.05). The results show that breast carcinoma cells, in addition to stromal cells, express iNOS and are capable of producing NO. Carcinomas with iNOS-positive tumor and stromal cells have a higher apoptotic indices and increased vascularization, suggesting that iNOS contributes to promotion of apoptosis and angiogenesis in breast carcinoma. The association of the number of iNOS-positive stromal cells with metastatic disease might be attributable to stimulation of angiogenesis, resulting in a higher vascular density and consequently a higher probability for tumor cells to invade.