The new old normal : reassessing perioperative oxygen consumption and haemodynamics in the elderly

Perioperative haemodynamic instability and disturbances of global oxygen transport are associated with complications and organ injury after surgery. The continuously growing population of elderly in surgical care are at higher risk due to age-related cardiovascular alterations and increased prevalence of comorbidities. Optimised and tailored haemodynamic interventions may improve outcomes, but goals to aim for and responses to expect are not adjusted for elderly. Hypotension and changes in oxygen consumption (VO2) induced by anaesthesia are potentially very relevant in the elderly and reassessment is needed in modern perioperative care with current methodologies. In this thesis, cardiac output and haemodynamic changes related to hypotension after spinal anaesthesia (SPA) are outlined in the first study. VO2 after general anaesthesia (GA) and surgery is investigated in three studies with different approaches; by meta-analysis, prospectively during major surgery and by method comparison. Study I (prospective observational): 20 ASA II-IV patients (mean age 72 years) were monitored with LiDCOTMplus prior to and 45 minutes after injection of SPA. Stroke volume and cardiac index, and consequently oxygen delivery index, decreased before the intrathecal injection and this decrease progressed after SPA in those who developed hypotension. In contrast, the non-hypotensive demonstrated an initial increase in cardiac index after SPA. Logistic regression analyses demonstrated that pre-anaesthetic changes of cardiac index could predict post-spinal hypotension (OR 0.79, 95% CI: 0.60, 0.91) with high discriminative ability (AUC 0.91). Study II (systematic review and meta-analysis): Cochrane Library, MEDLINE and EMBASE databases were searched for studies with measurements of VO2 before and after induction of GA. 24 studies with 453 patients were identified, published 1969-2000. Cochrane and NIH quality assessment tools revealed general high risk of bias in the majority of studies. However, measurements and interventions were described in great detail. A random-effects meta-analysis estimated the reduction of VO2 to -33 (95% CI: -38, -28) ml min-1 m-2 during GA but with uncertainty of the estimate due to very low quality as indicated in a GRADE evidence profile. A sample size calculation for study III was performed based on this data. Study III (prospective observational): VO2 was measured by indirect calorimetry (QuarkRMR), before, during and after major upper abdominal surgery in 20 ASA II-IV patients (mean age 73 years). VO2 decreased by a mean of -46 (95% CI: -55, -38) ml min-1 m-2 after induction of GA and increased during surgery. Simultaneous calculations of oxygen delivery (DO2) and estimated oxygen extraction ratio (O2ER) from LiDCOTMplus monitoring and arterial-central venous blood gas content showed low intraoperative levels of extraction and delivery. Mixed effect models of relative changes of intraoperative VO2 compared to DO2 and estimated O2ER indicated that these parameters changed in parallel. Study IV (method comparison): Estimations of VO2 by LiDCOTMplus-derived cardiac output and arterial-central venous oxygen content difference were compared to 85 simultaneous measurements by indirect calorimetry from study III. Intraclass correlation, Bland-Altman and mixed models analyses for relative changes over time indicated systematic underestimation and poor absolute agreement by this method compared to indirect calorimetry. It may be possible to construct methods for estimation or trending of VO2 from routine monitoring, but further adjustments and assessment in larger populations are needed. In summary, these studies characterise and demonstrate that peri-anaesthetic cardiac output and oxygen consumption undergo changes in elderly patients important to haemodynamic stability and oxygen transport. Mechanistic approaches, with feasible and reliable methods for monitoring or estimation of these changes, are suggested when investigating haemodynamic interventions in elderly. LIST OF SCIENTIFIC PAPERS I. Is postspinal hypotension a sign of impaired cardiac performance in the elderly? An observational mechanistic study Jakobsson J, Kalman, SH, Lindeberg-Lindvet M, Bartha E Br J Anaesth 2017; 119 (6): 1178-1185. II. The effects of general anaesthesia on oxygen consumption: A meta‐ analysis guiding future studies on perioperative oxygen transport Jakobsson, J, Vadman, S, Hagel, E, Kalman, S, Bartha, E Acta Anaesthesiol Scand 2019; 63: 144-53. E-pub Sept 20, 2018 III. Perioperative oxygen consumption revisited: An observational study in elderly undergoing major abdominal surgery Jakobsson J, Norén C, Hagel E, Kalman S, Bartha E Manuscript submitted for publication IV. Estimated oxygen consumption by minimal-invasive cardiac output and central venous sampling in major abdominal surgery: secondary outcomes of a prospective observational study in elderly Jakobsson J, Norén C, Hagel E, Backheden M, Kalman S, Bartha E Manuscript