- Comparison of Thrombelastography-Derived Fibrinogen Values at Rewarming and Following Cardiopulmonary Bypass in Cardiac Surgery Patients. [Journal Article]
- Anesth Analg 2016 Sep; 123(3):570-7.
The inflated costs and documented deleterious effects of excess perioperative transfusion have led to the investigation of targeted coagulation factor replacement strategies. One particular coagulation factor of interest is factor I (fibrinogen). Hypofibrinogenemia is typically tested for using time-consuming standard laboratory assays. The thrombelastography (TEG)-based functional fibrinogen level (FLEV) provides an assessment of whole blood clot under platelet inhibition to report calculated fibrinogen levels in significantly less time. If FLEV values obtained on cardiopulmonary bypass (CPB) during rewarming are similar to values obtained immediately after the discontinuation of CPB, then rewarming values could be used for preemptive ordering of appropriate blood product therapy.Fifty-one cardiac surgery patients were enrolled into this prospective nonrandomized study to compare rewarming fibrinogen values with postbypass values using TEG FLEV assays. Baseline, rewarming, and postbypass fibrinogen values were recorded for all patients using both standard laboratory assay (Clauss method) and FLEV. Mixed-effects regression models were used to examine the change in TEG FLEV values over time. Bland-Altman analysis was used to examine bias and the limits of agreement (LOA) between the standard laboratory assay and FLEVs.Forty-nine patients were included in the analysis. The mean FLEV value during rewarming was 333.9 mg/dL compared with 332.8 mg/dL after protamine, corresponding to an estimated difference of -1.1 mg/dL (95% confidence interval [CI], -25.8 to 23.6; P = 0.917). Rewarming values were available on average 47 minutes before postprotamine values. Bland-Altman analysis showed poor agreement between FLEV and standard assays: mean difference at baseline was 92.5 mg/dL (95% CI, 71.1 to 114.9), with a lower LOA of -56.5 mg/dL (95% CI, -94.4 to -18.6) and upper LOA of 242.4 mg/dL (95% CI, 204.5 to 280.3). The difference between assays increased after CPB and persisted after protamine administration.Our results revealed negligible change in FLEV values from the rewarming to postbypass periods, with a CI that does not include clinically meaningful differences. These findings suggest that rewarming samples could be utilized for ordering fibrinogen-specific therapies before discontinuation of CPB. Mean FLEV values were consistently higher than the reference standard at each time point. Moreover, bias was highly heterogeneous among samples, implying a large range of potential differences between assays for any 1 patient.
- Assessment of two alternative standardised tests for the vascular component of the hand-arm vibration syndrome (HAVS). [JOURNAL ARTICLE]
- Occup Environ Med 2016 Aug 17.
Vibration-induced white finger (VWF) is the vascular component of the hand-arm vibration syndrome (HAVS). Two tests have been standardised so as to assist the diagnosis of VWF: the measurement of finger rewarming times and the measurement of finger systolic blood pressures (FSBPs).This study investigates whether the two tests distinguish between fingers with and without symptoms of whiteness and compares individual results between the two test methods.In 60 men reporting symptoms of the HAVS, the times for their fingers to rewarm by 4°C (after immersion in 15°C water for 5 min) and FSBPs at 30°C, 15°C and 10°C were measured on the same day.There were significant increases in finger rewarming times and significant reductions in FSBPs at both 15°C and 10°C in fingers reported to suffer blanching. The FSBPs had sensitivities and specificities >90%, whereas the finger rewarming test had a sensitivity of 77% and a specificity of 79%. Fingers having longer rewarming times had lower FSBPs at both temperatures.The findings suggest that, when the test conditions are controlled according to the relevant standard, finger rewarming times and FSBPs can provide useful information for the diagnosis of VWF, although FSBPs are more sensitive and more specific.
- The Significance of Hypothermia in Abdominal Aortic Aneurysm Repair. [REVIEW, JOURNAL ARTICLE]
- Ann Vasc Surg 2016 Aug 13.
The aim was to review the literature on the association between hypothermia and outcomes in open and endovascular abdominal aortic aneurysm (AAA) repair. The secondary aim was to determine whether there is a difference in body temperature in patients undergoing either transperitoneal (TP), retroperitoneal (RP) or endovascular surgical repair of the abdominal aorta (EVAR).Literature review.MedLine, Web of Science and Trip searched for all studies on temperature in the context of aortic surgery or endovascular aortic interventions. In order to be included in the review, the papers had to be related to intraoperative or postoperative hypothermia and/or normothermia, with regards to either open or endovascular repair of the abdominal aorta. Thoracic or thoraco-abdominal aortic repairs were not included for review.Eight studies involving 765 patients were eligible. Of these, six studies looked at open elective AAA repair involving 605 patients. Only two studies investigated emergency AAA repair and consisted of 160 patients where only 35 of those patients underwent emergency EVAR. Normothermic patients had a shorter length of stay in the intensive care unit (P = 0.0008), while hypothermia was independently associated with higher rates of organ dysfunction, in-hospital mortality, and prolonged hospital length of stay. In ruptured AAAs, the lowest average intraoperative temperature was recorded in open repair compared to EVAR (P = 0.02). There was no statistically significant difference in postoperative temperature between patients undergoing elective RP repair and those having TP surgery.Studies have shown that hypothermia has numerous deleterious effects - whether or not these adverse outcomes are those such as higher rates of organ dysfunction, mortality or prolonged hospital length of stay, can only be done at the single paper level and not at a literature review level, due to multiple confounding variables. Despite these limitations, the benefits of this review are numerous. This paper highlights the importance of core body temperature and outcomes of AAA repair. Furthermore, it brings forth the need to standardize the method of core body temperature measurement and method of rewarming. Given the body of evidence so far, these standardized data collection points will be important for national vascular quality improvement initiatives. Only through rigorous analysis of standardized data set can firm recommendation regarding peri- and post operative temperature management be made.
- Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury. [Journal Article]
- Adv Exp Med Biol 2016.:245-51.
Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values <0.5, 0.5-1, >1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming.
- Evaluation of a novel in-line point-of-care blood gas analyser. [Journal Article]
- Anaesthesia 2016 Sep; 71(9):1044-52.
Point-of-care testing is becoming increasingly relevant to the practice of anaesthesia and critical care medicine, especially in terms of minimisation of sample volumes and decreased time to decision making. We performed a prospective observational study to evaluate a novel, in-line blood gas analysis device against a conventional benchtop model, and assessed it while placing the enrolled patients under extreme physiological conditions, specifically deep hypothermic circulatory arrest. Eight patients were studied, and had between seven and 11 samples analysed for seven variables (pH, pCO2 , pO2 , HCO3 (-) , base excess [BE], K(+) and haematocrit [Hct]), using the device during the process of cooling to 20 °C on cardiopulmonary bypass, and subsequent rewarming to normothermia. After Passing-Bablok analysis, the variables were evaluated for bias, limits of agreement and percentage error at above and below 30 °C. Of the measured variables, only pH (percentage error 2.4%) and potassium (19.8%) demonstrated acceptable (< 30%) percentage error over the full range of temperatures measured. Carbon dioxide, when stratified by temperature, was acceptable (< 30 °C percentage error 24.6%, > 30 °C percentage error 9.9%), but the overall percentage error of the dataset (45.8%) was excessively high. Bicarbonate and haematocrit both had an acceptable percentage error above 30 °C (25.2% and 18.5%, respectively), but similar to carbon dioxide, percentage error for the full range of temperatures exceeded 30%. These data differ from previous work examining this device, and highlights the difference between derived measures using different apparatuses when exposed to extreme physiological conditions.
- Black or white? Physiological implications of roost colour and choice in a microbat. [Journal Article]
- J Therm Biol 2016 Aug.:162-70.
Although roost choice in bats has been studied previously, little is known about how opposing roost colours affect the expression of torpor quantitatively. We quantified roost selection and thermoregulation in a captive Australian insectivorous bat, Nyctophilus gouldi (n=12) in winter when roosting in black and white coloured boxes using temperature-telemetry. We quantified how roost choice influences torpor expression when food was provided ad libitum or restricted in bats housed together in an outdoor aviary exposed to natural fluctuations of ambient temperature. Black box temperatures averaged 5.1°C (maximum 7.5°C) warmer than white boxes at their maximum daytime temperature. Bats fed ad libitum chose black boxes on most nights (92.9%) and on 100% of nights when food-restricted. All bats used torpor on all study days. However, bats fed ad libitum and roosting in black boxes used shorter torpor and spent more time normothermic/active at night than food-restricted bats and bats roosting in white boxes. Bats roosting in black boxes also rewarmed passively more often and to a higher skin temperature than those in white boxes. Our study suggests that N. gouldi fed ad libitum select warmer roosts in order to passively rewarm to a higher skin temperature and thus save energy required for active midday rewarming as well as to maintain a normothermic body temperature for longer periods at night. This study shows that colour should be considered when deploying bat boxes; black boxes are preferable for those bats that use passive rewarming, even in winter when food availability is reduced.
- Optimal temperature management in aortic arch operations. [REVIEW, JOURNAL ARTICLE]
- Gen Thorac Cardiovasc Surg 2016 Aug 8.
Hypothermic circulatory arrest is a critical component of aortic arch procedures, without which these operations could not be safely performed. Despite the use of hypothermia as a protective adjunct for organ preservation, aortic arch surgery remains complex and is associated with numerous complications despite years of surgical advancement. Deep hypothermic circulatory arrest affords the surgeon a safe period of time to perform the arch reconstruction, but this interruption of perfusion comes at a high clinical cost: stroke, paraplegia, and organ dysfunction are all potential-associated complications. Retrograde cerebral perfusion was subsequently developed as a technique to improve upon the rates of neurologic dysfunction, but was done with only modest success. Selective antegrade cerebral perfusion, on the other hand, has consistently been shown to be an effective form of cerebral protection over deep hypothermia alone, even during extended periods of circulatory arrest. A primary disadvantage of using deep hypothermic circulatory arrest is the prolonged bypass times required for cooling and rewarming which adds significantly to the morbidity associated with these procedures, especially coagulopathic bleeding and organ dysfunction. In an effort to mitigate this problem, the degree of hypothermia at the time of the initial circulatory arrest has more recently been reduced in multiple centers across the globe. This technique of moderate hypothermic circulatory arrest in combination with adjunctive brain perfusion techniques has been shown to be safe when performing aortic arch operations. In this review, we will discuss the evolution of these protection strategies as well as their relative strengths and weaknesses.
- A Brief Period of Hypothermia Induced by Total Liquid Ventilation Decreases End-Organ Damage and Multiorgan Failure Induced by Aortic Cross-Clamping. [Journal Article]
- Anesth Analg 2016 Sep; 123(3):659-69.
In animal models, whole-body cooling reduces end-organ injury after cardiac arrest and other hypoperfusion states. The benefits of cooling in humans, however, are uncertain, possibly because detrimental effects of prolonged cooling may offset any potential benefit. Total liquid ventilation (TLV) provides both ultrafast cooling and rewarming. In previous reports, ultrafast cooling with TLV potently reduced neurological injury after experimental cardiac arrest in animals. We hypothesized that a brief period of rapid cooling and rewarming via TLV could also mitigate multiorgan failure (MOF) after ischemia-reperfusion induced by aortic cross-clamping.Anesthetized rabbits were submitted to 30 minutes of supraceliac aortic cross-clamping followed by 300 minutes of reperfusion. They were allocated either to a normothermic procedure with conventional ventilation (control group) or to hypothermic TLV (33°C) before, during, and after cross-clamping (pre-clamp, per-clamp, and post-clamp groups, respectively). In all TLV groups, hypothermia was maintained for 75 minutes and switched to a rewarming mode before resumption to conventional mechanical ventilation. End points included cardiovascular, renal, liver, and inflammatory parameters measured 300 minutes after reperfusion.In the normothermic (control) group, ischemia-reperfusion injury produced evidence of MOF including severe vasoplegia, low cardiac output, acute kidney injury, and liver failure. In the TLV group, we observed gradual improvements in cardiac output in post-clamp, per-clamp, and pre-clamp groups versus control (53 ± 8, 64 ± 12, and 90 ± 24 vs 36 ± 23 mL/min/kg after 300 minutes of reperfusion, respectively). Liver biomarker levels were also lower in pre-clamp and per-clamp groups versus control. However, acute kidney injury was prevented in pre-clamp, and to a limited extent in per-clamp groups, but not in the post-clamp group. For instance, creatinine clearance was 4.8 ± 3.1 and 0.5 ± 0.6 mL/kg/min at the end of the follow-up in pre-clamp versus control animals (P = .0004). Histological examinations of the heart, kidney, liver, and jejunum in TLV and control groups also demonstrated reduced injury with TLV.A brief period of ultrafast cooling with TLV followed by rapid rewarming attenuated biochemical and histological markers of MOF after aortic cross-clamping. Cardiovascular and liver dysfunctions were limited by a brief period of hypothermic TLV, even when started after reperfusion. Conversely, acute kidney injury was limited only when hypothermia was started before reperfusion. Further work is needed to determine the clinical significance of our results and to identify the optimal duration and timing of TLV-induced hypothermia for end-organ protection in hypoperfusion states.
- Synchronizing Progression of Schizosaccharomyces pombe Cells from Prophase through Mitosis and into S Phase with nda3-KM311 Arrest Release. [Journal Article]
- Cold Spring Harb Protoc 2016; 2016(8):pdb.prot091256.
Here, we describe how the rapid reversibility of the nda3-KM311 cold-sensitive β-tubulin mutation was optimized by Mitsuhiro Yanagida's laboratory to synchronize mitotic progression in an entire cell population. The inability to form microtubules following the loss of β-tubulin function at 20°C triggers the spindle assembly checkpoint, which arrests mitotic progression. Restoration of β-tubulin function by rewarming to 30°C (or higher) releases the arrest, generating a highly synchronous progression through mitosis. The viability of nda3-KM311 strains at 30°C makes it feasible to generate double mutants between nda3-KM311 and any temperature-sensitive mutant that can also grow at 30°C. These double mutants can be used in reciprocal shift analyses, in which cold-induced early mitotic arrest is relieved by a shift to 36°C, which then inactivates the product of the second mutant gene. The addition of microtubule depolymerizing drugs before the return to 36°C will maintain checkpoint signaling at 36°C transiently, permitting analysis of the impact of temperature-sensitive mutations on checkpoint function. Silencing the checkpoint of nda3-KM311-arrested cells at 20°C through chemical inhibition of aurora kinase is a powerful way to study checkpoint recovery pathways and mitotic exit without anaphase.
- Profound accidental hypothermia - systematic approach to active recognition and treatment. [JOURNAL ARTICLE]
- ASAIO J 2016 Jul 26.
We sought to organize a functional system of recognition and advanced treatment of hypothermic patients with extracorporeal rewarming as a treatment option. All patients with suspected hypothermia are consulted with the Hypothermia Coordinator (HC), whose role is to provide expertise on hypothermia recognition and treatment to all rescue and medical services. Patients with Swiss Staging System of Hypothermia (HT) class III and IV are subjected to extracorporeal rewarming. Patients with class I and II are managed in local hospitals, after the hypothermia coordinator provides instructions.From program initiation (July 29, 2013) to November 1, 2015, HC consulted 104 hypothermic patients; 21 in HT class III and IV were subjected to extracorporeal rewarming in the John Paul II Hospital in Cracow, Poland. The remaining individuals were rewarmed in the referring hospitals. Cardiac arrest upon referral was present in 10 cases (resuscitation times from arrest to ECMO implantation ranged 107-345 minutes). Seven patients died, the remaining 14 have been rewarmed with the restoration of hemodynamic stability. Systematic approach to active recognition and treatment of profound accidental hypothermia patients, based on HC cooperation with emergency medical services enables advanced management with good outcomes, especially in patients with cardiac arrest.