A novel continuous capnodynamic method for cardiac output assessment in a porcine model of lung lavage.

BACKGROUND: We have evaluated a new method for continuous monitoring of effective pulmonary blood flow (COEPBF ), i.e. cardiac output (CO) minus intra-pulmonary shunt, during mechanical ventilation. The method has shown good trending ability during severe hemodynamic challenges in a porcine model with intact lungs. In this study, we further evaluate the COEPBF method in a model of lung lavage. METHODS: COEPBF was compared to a reference method for CO during hemodynamic and PEEP alterations, 5 and 12 cmH2 O, before and after repeated lung lavages in 10 anaesthetised pigs. Bland-Altman, four-quadrant and polar plot methodologies were used to determine agreement and trending ability. RESULTS: After lung lavage at PEEP 5 cmH2 O, the ratio of arterial oxygen partial pressure related to inspired fraction of oxygen significantly decreased. The mean difference (limits of agreement) between methods changed from 0.2 (-1.1 to 1.5) to -0.9 (-3.6 to 1.9) l/min and percentage error increased from 34% to 70%. Trending ability remained good according to the four-quadrant plot (concordance rate 94%), whereas mean angular bias increased from 4° to -16° when using the polar plot methodology. CONCLUSION: Both agreement and precision of COEPBF were impaired in relation to CO when the shunt fraction was increased after lavage at PEEP 5 cmH2 O. However, trending ability remained good as assessed by the four-quadrant plot, whereas the mean polar angle, calculated by the polar plot, was wide.

Cognitive testing with the Post-Operative Quality of Recovery Scale in pre-surgery cancer patients--a controlled study.

BACKGROUND: Post-Operative Quality of Recovery Scale (PQRS) has been revised to allow for the normal variation in cognitive performance seen in healthy volunteers. This modification could result in exclusion of test subjects because of poor baseline performance. Our aim was to investigate the impact of severe disease and waiting for cancer surgery on PQRS baseline cognitive performance and exclusion rate, and also on variation in cognitive performance at test re-test. METHODS: Sixty-one subjects, 31 women diagnosed with breast cancer and waiting for surgery and 30 healthy women, performed the PQRS cognitive, nociceptive and emotional domains three times in 48 h. Exclusion rate, change in score and the proportion fulfilling 'recovery' criteria at re-tests were assessed. RESULTS: Nine out of 31 patients (29%) and two out of 30 controls (7%) had too low baseline score to be further assessed (P = 0.043). The change in score at re-tests was similar between the groups. Sixty-four per cent and 83% at 20 h and 79% and 86% at 48 h in the patient and control groups respectively fulfilled the 'recovery' criteria (P = 0.45). The 'recovery' for nociceptive and emotional distress was similar between the groups, but anxiety and sadness absolute scores were significantly higher in the patient group. CONCLUSION: Women with breast cancer waiting for surgery expressed a higher level of emotional distress, performed lower at baseline but showed no difference in test re-test variability in cognitive performance according to the PQRS when compared with controls. The considerable exclusion rate among patients waiting for cancer surgery should be acknowledged.

Cognitive recovery after ambulatory anaesthesia based on desflurane or propofol: a prospective randomised study.

BACKGROUND: The impact of anaesthetic agents on cognitive recovery during the first post-operative week in a middle-aged population undergoing general anaesthesia is insufficiently studied. We hypothesised that patients receiving anaesthesia based on desflurane would have a quicker recovery and regain cognitive capacity faster than patients receiving anaesthesia based on propofol. METHODS: We performed a prospective, randomised, single-blinded study comparing the effects of desflurane and propofol as primary anaesthetic agents on cognitive recovery in 59 American Society of Anesthesiologists Physical Status Classification System I-II women undergoing breast surgery. Cognitive recovery was evaluated using the Cognitive Failure Questionnaire and a modified version of the Post-operative Quality of Recovery Scale. RESULTS: Post-operative cognitive recovery according to Cognitive Failure Questionnaire was 65% and 66% at 72 h, and 71% and 72% at 1 week for the desflurane and the propofol groups, respectively. Recovery according to Post-operative Quality of Recovery Scale was 52% and 50% at 2 h, increasing to 71% and 87% at 48 h for the desflurane and the propofol groups, respectively. At the final point of measurement (Cognitive Failure Questionnaire 1 week, Post-operative Quality of Recovery Scale 48 h), many of the patients had still not reached their baseline cognitive performance. There was no difference in overall cognitive recovery between the desflurane and propofol groups. CONCLUSION: Cognitive recovery was not complete 1 week after surgery in any of the groups. There was no difference in the rate of cognitive recovery in middle-aged patients receiving desflurane or propofol anaesthesia during ambulatory breast surgery.

Novel continuous capnodynamic method for cardiac output assessment during mechanical ventilation.

BACKGROUND: It is important to be able to accurately monitor cardiac output (CO) during high-risk surgery and in critically ill patients. The invasiveness of the pulmonary artery catheter (PAC) limits its use, and therefore, new minimally invasive methods for CO monitoring are needed. A potential method is estimation of CO from endogenous carbon dioxide measurements, using a differentiated Fick's principle to determine effective pulmonary blood flow (EPBF). In this study, we aimed to validate a novel capnodynamic method (COEPBF) in a wide range of clinically relevant haemodynamic conditions. METHODS: COEPBF was studied in 10 pigs during changes in preload, afterload, CO increase, and bleeding. An ultrasonic flow probe around the pulmonary artery was used as reference method of CO determination. CO was also measured using a PAC thermodilution technique (COPAC). CO and other haemodynamic data were recorded before and during each intervention. Accuracy and precision and also the ability to track changes in CO were determined using Bland-Altman, four-quadrant plot and polar plot analysis. RESULTS: COEPBF and COPAC showed equally good agreement, with a tendency to overestimate CO (bias 0.2 and 0.3 litre min(-1), respectively). The overall percentage error was 47% for COEPBF and 49% for COPAC. The concordance for tracking CO changes was 97 and 95% for COEPBF and COPAC, respectively, with an exclusion zone of 15% and radial limits of ±30°. CONCLUSIONS: COEPBF showed reliable trending abilities, equivalent to COPAC. COEPBF and COPAC also showed low bias but high percentage errors. Further studies in animal models of lung injury and in high-risk surgery patients are warranted.

Stroke volume optimization in elective bowel surgery: a comparison between pulse power wave analysis (LiDCOrapid) and oesophageal Doppler (CardioQ).

BACKGROUND: Goal-directed fluid therapy improves outcome in major surgery. We evaluated a new device (LiDCOrapid) against our standard oesophageal Doppler method (ODM) for stroke volume (SV) optimization during colorectal surgery. METHODS: This was an observational study in 20 patients undergoing major colorectal surgery within a fast-track protocol. We compared SV values measured simultaneously by LiDCOrapid and ODM before and after 86 fluid challenges. We also evaluated the LiDCOrapid dynamic indices SV variation (SVV) and pulse pressure variation (PPV) as predictors for volume responsiveness, defined as an increase in SV ≥ 10% after 200 ml of colloid. RESULTS: SV increased ≥ 10% after 27 out of 86 fluid challenges. For 172 paired SV values, the overall correlation was r=0.39, and bias (limits of agreement) -28 (-91-35) ml, percentage error 70%. The ability of LiDCOrapid to track changes in SV was weak with a concordance rate of 80%, and a sensitivity and specificity of 48% and 81%, respectively, to detect a positive fluid challenge. The area under the curve values (with 95% confidence intervals) for SVV and PPV were 0.72 (0.60-0.83) and 0.66 (0.52-0.79), respectively, indicating low predictive capacity in these setting. CONCLUSIONS: LiDCOrapid and ODM devices are not interchangeable. We cannot recommend that the LiDCOrapid replace the standard Doppler method until further device-specific outcome studies on volume optimization are available. The dynamic indices SVV and PPV add little value to a fluid optimization protocol, and should not replace SV measurements with a validated technique.

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness.

Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to NO and related compounds, which have potential biological activity. We used an in vivo rat model as a bioassay to test effects of human saliva on gastric mucosal blood flow and mucus thickness. Gastric mucosal blood flow and mucus thickness were measured after topical administration of human saliva in HCl. The saliva was collected either after fasting (low in nitrite) or after ingestion of sodium nitrate (high in nitrite). In additional experiments, saliva was exchanged for sodium nitrite at different doses. Mucosal blood flow was increased after luminal application of nitrite-rich saliva, whereas fasting saliva had no effects. Also, mucus thickness increased in response to nitrite-rich saliva. The effects of nitrite-rich saliva were similar to those of topically applied sodium nitrite. Nitrite-mediated effects were associated with generation of NO and S-nitrosothiols. In addition, pretreatment with an inhibitor of guanylyl cyclase markedly inhibited nitrite-mediated effects on blood flow. We conclude that nitrite-containing human saliva given luminally increases gastric mucosal blood flow and mucus thickness in the rat. These effects are likely mediated through nonenzymatic generation of NO via activation of guanylyl cyclase. This supports a gastroprotective role of salivary nitrate/nitrite.

Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation.

The fundamental, yet poorly understood, physiological mechanism known as 'acidic-metabolic' vasodilation, contributes to local blood flow regulation during hypoxia/ischaemia and increased metabolic activity. The vasodilator nitric oxide (NO) has been suggested to be involved in this event. Besides enzymatic production by NO synthases, a novel mechanism for generation of this gas in vivo was recently described. This involves non-enzymatic reduction of inorganic nitrite to NO, a reaction that takes place predominantly during acidic/reducing conditions. We have studied the effects of physiological amounts of nitrite on NO generation and relaxation of rat aorta in vitro in a situation where environmental pH was reduced to levels seen in tissues during hypoxia/ischaemia. The relaxatory effect of nitrite was increased in an acidic buffer solution (pH 6.6) compared with neutral pH; EC50 for nitrite was reduced from 200 to 40 microM. Nitrite-evoked relaxation was effectively prevented by coadministration of an inhibitor of soluble guanylyl cyclase. The relaxation was further potentiated by the addition of ascorbic acid. In parallel, NO was generated from nitrite in a pH dependent manner with even larger amounts seen after addition of ascorbic acid. NO generation from nitrite correlated to the the degree of relaxation of rat aorta. These results illustrate non-enzymatic release of NO from nitrite at physiological concentrations. This may be an important auto-regulated physiological mechanism involved in the regulation of vascular tone during hypoxia/ischaemia.

Nitric oxide inhibition of renal vasoconstrictor responses to sympathetic cotransmitters in the pig in vivo.

The object of the present study was to investigate the involvement of nitric oxide (NO) in the regulation of renal vasoconstrictor responses to sympathetic nerve activation, and each of the known sympathetic cotransmitters separately, in the pig in vivo. Renal vasoconstrictor responses were elicited by sympathetic nerve stimulation, the alpha(1)-adrenoceptor agonist phenylephrine (10 nmol kg(-1), injected iv), neuropeptide Y (NPY, 120 pmol kg(-1), iv) acting on the NPY Y(1) receptor, and the stable ATP-analogue alpha,beta-methylene ATP (mATP, 10 nmol kg(-1)) presumably acting on the P2X(1) purinoceptor. Infusion of the NO-donor sodium nitroprusside, at a dose (0.1 mg kg(-1) h(-1), iv) that elevated renal blood flow (by 14 +/- 7%) and lowered mean arterial pressure (by 30 +/- 5%), inhibited renal vasoconstrictor responses to sympathetic nerve stimulation, phenylephrine, and NPY, but not to mATP. In contrast, injection of the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, at a dose (10 mg kg(-1), iv) that lowered renal blood flow (by 47 +/- 4%) and elevated mean arterial pressure (by 28 +/- 8%), potentiated the renal vasoconstriction evoked by sympathetic nerve stimulation, phenylephrine, and NPY, but not mATP. It is concluded that endogenous NO may function as an inhibitory modulator of vasoconstrictor responses to the sympathetic cotransmitters norepinephrine and NPY. In contrast, NO seems not to modify vasoconstrictor responses to the sympathetic cotransmitter ATP, a discrepancy that may be due to differences in the types of receptors and intracellular effector mechanisms.