Efficacy of a pre-operative anaemia clinic in patients undergoing elective abdominal cancer surgery.

BACKGROUND: Pre-operative iron deficiency anaemia (IDA) is common in patients undergoing elective major abdominal surgery and is associated with increased risk of perioperative complications. However, widespread implementation of pre-operative anaemia management is lacking. Guidelines recommend investigation of anaemia preferably 4-6 weeks before surgery to allow time for correction. However, this is not always feasible in abdominal cancer surgery with short time to surgery and may be influenced by concomitant chemotherapy. The objective of this study was to assess the efficacy of implementing a pre-operative screening and treatment programme for IDA in elective abdominal cancer surgery patients, with short duration to surgery and concomitant use of chemotherapy. METHODS: All patients scheduled for elective abdominal cancer surgery with IDA were included. Anaemia was defined according to the World Health Organization-criteria and iron deficiency as a transferrin saturation <0.20. The primary outcome was change in haemoglobin (Hb) between iron infusion and surgery in patients receiving pre-operative intravenous iron infusion. RESULTS: Of 178 diagnosed IDA patients 134 (75%) received intravenous iron, 103 pre-operatively (58%) at median day 17 (interquartile range: 9-27) before surgery while 31 (17%) received post-operative intravenous iron treatment. The pre-operative Hb increased 0.89 g/dL (95% CI: 0.64-1.13, p < .001) compared to a decrease of 0.4 g/dL (95% CI: 0.19-0.58, p < .001) in 75 patients not treated pre-operatively. Patients diagnosed with severe anaemia had the largest pre-operative Hb increase. Iron infusion >2 weeks pre-operatively resulted in a greater Hb increment of 1.13 g/dL (95% CI: 0.81-1.45) compared to iron infusion ≤2 weeks before surgery 0.48 g/dL (95% CI: 0.16-0.81). Hb increased by 0.64 g/dL (95% CI 0.19-1.21) in patients receiving chemotherapy ≤31 days prior to surgery. CONCLUSION: In patients scheduled for abdominal cancer surgery, including in patients with concomitant chemotherapy, pre-operative IDA management is feasible and results in a significant pre-operative Hb increase compared to patients not treated. On the day of surgery 25% patients treated pre-operatively were no longer anaemic.

Haemodynamic and respiratory perioperative outcomes for open versus robot-assisted radical cystectomy: A double-blinded, randomised trial.

BACKGROUND: The clinical impact of prolonged steep Trendelenburg position and CO2 pneumoperitoneum during robot-assisted radical cystectomy (RC) on intraoperative conditions and immediate postoperative recovery remains to be assessed. The current study investigates intraoperative and immediate postoperative outcomes for open RC (ORC) versus robot-assisted RC with intracorporal urinary diversion (iRARC) in a blinded randomised trial. We hypothesised that ORC would result in a faster haemodynamic and respiratory post-anaesthesia care unit (PACU) recovery compared to iRARC. METHODS: This study is a predefined sub-analysis of a single-centre, double-blinded, randomised feasibility study. Fifty bladder cancer patients were randomly assigned to ORC (n = 25) or iRARC (n = 25). Patients, PACU staff, and ward personnel were blinded to the surgical technique. Both randomisation arms followed the same anaesthesiologic procedure, fluid treatment plan, and PACU care. The primary outcome was immediate postoperative recovery using a standardised PACU Discharge Criteria (PACU-DC) score. Secondary outcomes included respiration- and arterial O2 saturation scores as well as perioperative interventions and recordings. RESULTS: All patients underwent the allocated treatment. The total PACU-DC score was highest 6 h postoperatively with no difference in the total score between randomisation arms (p = 0.80). Both the ORC and iRARC groups maintained a mean respiration- and arterial O2 saturation score below 1 (out of 3) throughout PACU stay. The iRARC patients had significantly, but clinically acceptable, higher maximum airway pressure and arterial blood pressure, as well as lower minimum pH levels. The ORC group received significantly more opioids after extubation but marginally less analgesics in the PACU, compared to the iRARC group. CONCLUSIONS: A prolonged Trendelenburg position and CO2 pneumoperitoneum was well-tolerated during iRARC, and immediate postoperative recovery was similar for ORC and iRARC patients.

Persistent severe post-operative hypotension after pancreaticoduodenectomy is related to increased inflammatory response.

BACKGROUND: Hypotension during major surgery is frequent, resulting in increased need for observation in the post-anaesthesia care unit and treatment including vasopressors and fluids. However, although severe hypotension in the immediate post-operative recovery phase after major surgery is suggested to be related to increased morbidity and mortality, the underlying risk factors are not well described, hindering advancements in prevention and treatment. METHODS: We performed a retrospective study assessing factors (age, gender, body-mass index, cardiac co-morbidity, haemoglobin, absolute and increase in c-reactive protein on the first post-operative day, bleeding, fluid balance at the end of surgery and the first post-operative day) related to severe persistent hypotension (SPH) (SPH: need for noradrenaline to maintain a mean arterial blood pressure (MAP) >65.0 mm Hg on the morning after surgery) and occurrence of other early (24 hours) complications. One hundred patients undergoing pancreaticoduodenectomy (PD) with pre-operative high-dose glucocorticoid and goal-directed fluid therapy were enrolled and perioperative data collected from anaesthetic and medical records. RESULTS: Forty-five patients had SPH, who had a significantly higher increase in CRP levels the morning after surgery (median 50 mg L-1 vs 41 mg L-1 , SPH vs non-SPH, respectively, P = .028), and a significantly more positive fluid balance at discharge (median 1457 ml vs 1031 ml, respectively, P = .027) vs patients without SPH. CONCLUSIONS: Severe persistent hypotension after PD was associated with significantly increased inflammatory response and increased need for fluids. Future studies should investigate the effect of further inflammatory control in PD to improve haemodynamics and morbidity.

Beneficial effects of elevating cardiac preload on left-ventricular diastolic function and volume during heat stress: implications toward tolerance during a hemorrhagic insult.

Volume loading normalizes tolerance to a simulated hemorrhagic challenge in heat-stressed individuals, relative to when these individuals are thermoneutral. The mechanism(s) by which this occurs is unknown. This project tested two unique hypotheses; that is, the elevation of central blood volume via volume loading while heat stressed would 1) increase indices of left ventricular diastolic function, and 2) preserve left ventricular end-diastolic volume (LVEDV) during a subsequent simulated hemorrhagic challenge induced by lower-body negative pressure (LBNP). Indices of left ventricular diastolic function were evaluated in nine subjects during the following conditions: thermoneutral, heat stress, and heat stress after acute volume loading sufficient to return ventricular filling pressures toward thermoneutral levels. LVEDV was also measured in these subjects during the aforementioned conditions prior to and during a simulated hemorrhagic challenge. Heat stress did not change indices of diastolic function. Subsequent volume infusion elevated indices of diastolic function, specifically early diastolic mitral annular tissue velocity (E') and early diastolic propagation velocity (E) relative to both thermoneutral and heat stress conditions (P < 0.05 for both). Heat stress reduced LVEDV (P < 0.05), while volume infusion returned LVEDV to thermoneutral levels. The reduction in LVEDV to LBNP was similar between thermoneutral and heat stress conditions, whereas the reduction after volume infusion was attenuated relative to both conditions (P < 0.05). Absolute LVEDV during LBNP after volume loading was appreciably greater relative to the same level of LBNP during heat stress alone. Thus, rapid volume infusion during heat stress increased indices of left ventricular diastolic function and attenuated the reduction in LVEDV during LBNP, both of which may serve as mechanisms by which volume loading improves tolerance to a combined hyperthermic and hemorrhagic challenge.

Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial.

BACKGROUND: Early mobilization is important for postoperative recovery but is limited by orthostatic intolerance (OI) with a prevalence of 50% 6 h after major surgery. The pathophysiology of postoperative OI is assumed to include hypovolemia besides dysregulation of vasomotor tone. Stroke volume-guided fluid therapy, so-called goal-directed therapy (GDT), corrects functional hypovolemia, and the authors hypothesized that GDT reduces the prevalence of OI after major surgery and assessed this in a prospective, double-blinded trial. METHODS: Forty-two patients scheduled for open radical prostatectomy were randomized into standard fluid therapy (control group) or GDT groups. Both groups received a fixed-volume crystalloid regimen supplemented with 1:1 replacement of blood loss with colloid, and in addition, the GDT group received colloid to obtain a maximal stroke volume (esophageal Doppler). The primary outcome was the prevalence of OI assessed with a standardized mobilization protocol before and 6 h after surgery. Hemodynamic and hormonal orthostatic responses were evaluated. RESULTS: Twelve (57%) versus 15 (71%) patients in the control and GDT groups (P = 0.33), respectively, demonstrated OI after surgery, group difference 14% (CI, -18 to 45%). Patients in the GDT group received more colloid during surgery (1,758 vs. 1,057 ml; P = 0.001) and reached a higher stroke volume (102 vs. 89 ml; P = 0.04). OI patients had an increased length of hospital stay (3 vs. 2 days; P = 0.02) and impaired hemodynamic and norepinephrine responses on mobilization. CONCLUSION: GDT did not reduce the prevalence of OI, and patients with OI demonstrated impaired cardiovascular and hormonal responses to mobilization.

Acute volume expansion attenuates hyperthermia-induced reductions in cerebral perfusion during simulated hemorrhage.

Hyperthermia reduces the capacity to withstand a simulated hemorrhagic challenge, but volume loading preserves this capacity. This study tested the hypotheses that acute volume expansion during hyperthermia increases cerebral perfusion and attenuates reductions in cerebral perfusion during a simulated hemorrhagic challenge induced by lower-body negative pressure (LBNP). Eight healthy young male subjects underwent a supine baseline period (pre-LBNP), followed by 15- and 30-mmHg LBNP while normothermic, hyperthermic (increased pulmonary artery blood temperature ~1.1°C), and following acute volume infusion while hyperthermic. Primary dependent variables were mean middle cerebral artery blood velocity (MCAvmean), serving as an index of cerebral perfusion; mean arterial pressure (MAP); and cardiac output (thermodilution). During baseline, hyperthermia reduced MCAvmean (P = 0.001) by 12 ± 9% relative to normothermia. Volume infusion while hyperthermic increased cardiac output by 2.8 ± 1.4 l/min (P < 0.001), but did not alter MCAvmean (P = 0.99) or MAP (P = 0.39) compared with hyperthermia alone. Relative to hyperthermia, at 30-mmHg LBNP acute volume infusion attenuated reductions (P < 0.001) in cardiac output (by 2.5 ± 0.9 l/min; P < 0.001), MAP (by 5 ± 6 mmHg; P = 0.004), and MCAvmean (by 12 ± 13%; P = 0.002). These data indicate that acute volume expansion does not reverse hyperthermia-induced reductions in cerebral perfusion pre-LBNP, but that it does attenuate reductions in cerebral perfusion during simulated hemorrhage in hyperthermic humans.

[Early post-operative mobilization and orthostatic intolerance]. / Tidlig postoperativ mobilisering og ortostatisk intolerans.

Early mobilization after surgery is crucial for an enhanced recovery and can reduce complications associated with immobility. Symptoms such as nausea, vomiting, blurred vision and dizziness are however known to impede early mobilization. Together these symptoms comprise orthostatic intolerance (OI), in which the ultimate manifestation is syncope. In reference to find preventive and relevant treatment for OI studies with a multimodal approach have shown promising results, though the pathophysiology behind OI is not fully understood.

Modelflow underestimates cardiac output in heat-stressed individuals.

An estimation of cardiac output can be obtained from arterial pressure waveforms using the Modelflow method. However, whether the assumptions associated with Modelflow calculations are accurate during whole body heating is unknown. This project tested the hypothesis that cardiac output obtained via Modelflow accurately tracks thermodilution-derived cardiac outputs during whole body heat stress. Acute changes of cardiac output were accomplished via lower-body negative pressure (LBNP) during normothermic and heat-stressed conditions. In nine healthy normotensive subjects, arterial pressure was measured via brachial artery cannulation and the volume-clamp method of the Finometer. Cardiac output was estimated from both pressure waveforms using the Modeflow method. In normothermic conditions, cardiac outputs estimated via Modelflow (arterial cannulation: 6.1 ± 1.0 l/min; Finometer 6.3 ± 1.3 l/min) were similar with cardiac outputs measured by thermodilution (6.4 ± 0.8 l/min). The subsequent reduction in cardiac output during LBNP was also similar among these methods. Whole body heat stress elevated internal temperature from 36.6 ± 0.3 to 37.8 ± 0.4°C and increased cardiac output from 6.4 ± 0.8 to 10.9 ± 2.0 l/min when evaluated with thermodilution (P < 0.001). However, the increase in cardiac output estimated from the Modelflow method for both arterial cannulation (2.3 ± 1.1 l/min) and Finometer (1.5 ± 1.2 l/min) was attenuated compared with thermodilution (4.5 ± 1.4 l/min, both P < 0.01). Finally, the reduction in cardiac output during LBNP while heat stressed was significantly attenuated for both Modelflow methods (cannulation: -1.8 ± 1.2 l/min, Finometer: -1.5 ± 0.9 l/min) compared with thermodilution (-3.8 ± 1.19 l/min). These results demonstrate that the Modelflow method, regardless of Finometer or direct arterial waveforms, underestimates cardiac output during heat stress and during subsequent reductions in cardiac output via LBNP.

Normovolemia defined according to cardiac stroke volume in healthy supine humans.

BACKGROUND: Both hypovolemia and a fluid overload are detrimental for outcome in surgical patients but the effort to establish normovolemia is hampered by the lack of an operational clinical definition. Manipulating the central blood volume on a tilt table demonstrates that the flat part of the Frank-Starling curve is reached when subjects are supine and that finding may be applicable for a clinical definition of normovolemia. However, it is unknown whether stroke volume (SV) responds to an increase in preload induced by fluid administration. METHODS: In 20 healthy subjects (23 +/- 2 years, mean +/- SD), SV was measured by esophageal Doppler before and after fluid administration to evaluate whether SV increases in healthy, non-fasting, supine subjects. Two hundred millilitres of a synthetic colloid (hydroxyethyl starch, HES 130/0.4) was provided and repeated if a >or=10% increment in SV was obtained. RESULTS: None of the subjects increased SV >or=10% following fluid administration but there was a minor increase in mean arterial pressure (92 +/- 15 to 93 +/- 12 mmHg, P = 0.01), while heart rate (HR) (66 +/- 12 beats min(-1); P = 0.32), cardiac output (4.8 +/- 1.1 l min(-1); P = 0.25) and the length of the systole corrected to a HR of 60 beats/min (corrected flow time; 344 +/- 24 ms; P = 0.31) did not change. CONCLUSION: Supporting the proposed definition of normovolemia, non-fasting, supine, healthy subjects are provided with a preload to the heart that does not limit SV suggesting that the upper flat part of the Frank-Starling relationship is reached.

A definition of normovolaemia and consequences for cardiovascular control during orthostatic and environmental stress.

The Frank-Starling mechanism describes the relationship between stroke volume and preload to the heart, or the volume of blood that is available to the heart--the central blood volume. Understanding the role of the central blood volume for cardiovascular control has been complicated by the fact that a given central blood volume may be associated with markedly different central vascular pressures. The central blood volume varies with posture and, consequently, stroke volume and cardiac output (Q) are affected, but with the increased central blood volume during head-down tilt, stroke volume and Q do not increase further indicating that in the supine resting position the heart operates on the plateau of the Frank-Starling curve which, therefore, may be taken as a functional definition of normovolaemia. Since the capacity of the vascular system surpasses the blood volume, orthostatic and environmental stress including bed rest/microgravity, exercise and training, thermal loading, illness, and trauma/haemorrhage is likely to restrict venous return and Q. Consequently the cardiovascular responses are determined primarily by their effect on the central blood volume. Thus during environmental stress, flow redistribution becomes dependent on sympathetic activation affecting not only skin and splanchnic blood flow, but also flow to skeletal muscles and the brain. This review addresses the hypothesis that deviations from normovolaemia significantly influence these cardiovascular responses.

Techniques of cardiac output measurement during liver transplantation: arterial pulse wave versus thermodilution.

In this study, we compared continuous cardiac output (CO) obtained from the femoral arterial pressure by simulation of an aortic input impedance model [model-simulated cardiac output (MCO)] to thermodilution cardiac output (TDCO) determined by bolus injection during liver transplantation. Both variables were measured in 39 adult patients (13 females) every 10th minute during liver transplant surgery. Paired measurements were compared during the 4 phases of surgery-dissection, anhepatic phase, early reperfusion (the first 15 minutes after reperfusion), and late reperfusion (15-60 minutes after reperfusion)-without the detection of any significant difference between the 2 estimates of CO. TDCO ranged from 2.3 to 17.2 L/minute, and the bias (the mean difference between MCO and TDCO) prior to calibration was -0.4 +/- 1.6 L/minute (mean +/- standard deviation; 1309 paired measurements; 95% limits of agreement: -3.4 to 2.6 L/minute). After calibration of the first determined MCO by the simultaneously determined TDCO, the bias was 0.1 +/- 1.5 L/minute, with 57% (n = 744) of the comparisons being less than 1 L/minute and 35% (n = 453) being less than 0.5 L/minute; this was independent of the level of CO, and the mutual correlation coefficient was 0.812 (P < 0.001). This study indicates that during liver transplantation surgery, MCO reflects TDCO throughout the operation. Thus, for CO, this less invasive method appears to provide a reliable uninterrupted measurement during orthotopic liver transplantation.