An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence.

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.

Subtle ocular movements in a patient with brain death.

Introduction and Case Presentation: Brain death can be associated with limb movements that are attributed to spinal reflexes. Although head/face movements have been rarely reported, no case of overt eye movements in brain death has been documented. We report a case of a patient with subtle eye movements whose exam was otherwise consistent with brain death. The presence of eye movements delayed pronouncing the patient as brain dead and delayed organ donation. We agree with American Academy of Neurology Position statement from 2019 that brain death does not mean demise of every neuron. Discussion: This case raises important questions about the types of movements that should be "allowed" during the determination of brain death to avoid delays in diagnosis.

Ultrasound-guided vascular access in critical illness.

Over the past two decades, ultrasound (US) has become widely accepted to guide safe and accurate insertion of vascular devices in critically ill patients. We emphasize central venous catheter insertion, given its broad application in critically ill patients, but also review the use of US for accessing peripheral veins, arteries, the medullary canal, and vessels for institution of extracorporeal life support. To ensure procedural safety and high cannulation success rates we recommend using a systematic protocolized approach for US-guided vascular access in elective clinical situations. A standardized approach minimizes variability in clinical practice, provides a framework for education and training, facilitates implementation, and enables quality analysis. This review will address the state of US-guided vascular access, including current practice and future directions.

Is ice-rafted sediment in a North Pole marine record evidence for perennial sea-ice cover?

Ice-rafted sediments of Eurasian and North American origin are found consistently in the upper part (13 Ma BP to present) of the Arctic Coring Expedition (ACEX) ocean core from the Lomonosov Ridge, near the North Pole (≈88° N). Based on modern sea-ice drift trajectories and speeds, this has been taken as evidence of the presence of a perennial sea-ice cover in the Arctic Ocean from the middle Miocene onwards (Krylov et al. 2008 Paleoceanography 23, PA1S06. (doi:10.1029/2007PA001497); Darby 2008 Paleoceanography 23, PA1S07. (doi:10.1029/2007PA001479)). However, other high latitude land and marine records indicate a long-term trend towards cooling broken by periods of extensive warming suggestive of a seasonally ice-free Arctic between the Miocene and the present (Polyak et al. 2010 Quaternary Science Reviews 29, 1757-1778. (doi:10.1016/j.quascirev.2010.02.010)). We use a coupled sea-ice slab-ocean model including sediment transport tracers to map the spatial distribution of ice-rafted deposits in the Arctic Ocean. We use 6 hourly wind forcing and surface heat fluxes for two different climates: one with a perennial sea-ice cover similar to that of the present day and one with seasonally ice-free conditions, similar to that simulated in future projections. Model results confirm that in the present-day climate, sea ice takes more than 1 year to transport sediment from all its peripheral seas to the North Pole. However, in a warmer climate, sea-ice speeds are significantly faster (for the same wind forcing) and can deposit sediments of Laptev, East Siberian and perhaps also Beaufort Sea origin at the North Pole. This is primarily because of the fact that sea-ice interactions are much weaker with a thinner ice cover and there is less resistance to drift. We conclude that the presence of ice-rafted sediment of Eurasian and North American origin at the North Pole does not imply a perennial sea-ice cover in the Arctic Ocean, reconciling the ACEX ocean core data with other land and marine records.

Consistent simulations of multiple proxy responses to an abrupt climate change event.

Isotope, aerosol, and methane records document an abrupt cooling event across the Northern Hemisphere at 8.2 kiloyears before present (kyr), while separate geologic lines of evidence document the catastrophic drainage of the glacial Lakes Agassiz and Ojibway into the Hudson Bay at approximately the same time. This melt water pulse may have been the catalyst for a decrease in North Atlantic Deep Water formation and subsequent cooling around the Northern Hemisphere. However, lack of direct evidence for ocean cooling has lead to speculation that this abrupt event was purely local to Greenland and called into question this proposed mechanism. We simulate the response to this melt water pulse using a coupled general circulation model that explicitly tracks water isotopes and with atmosphere-only experiments that calculate changes in atmospheric aerosol deposition (specifically (10)Be and dust) and wetland methane emissions. The simulations produce a short period of significantly diminished North Atlantic Deep Water and are able to quantitatively match paleoclimate observations, including the lack of isotopic signal in the North Atlantic. This direct comparison with multiple proxy records provides compelling evidence that changes in ocean circulation played a major role in this abrupt climate change event.

Amplification of surface temperature trends and variability in the tropical atmosphere.

The month-to-month variability of tropical temperatures is larger in the troposphere than at Earth's surface. This amplification behavior is similar in a range of observations and climate model simulations and is consistent with basic theory. On multidecadal time scales, tropospheric amplification of surface warming is a robust feature of model simulations, but it occurs in only one observational data set. Other observations show weak, or even negative, amplification. These results suggest either that different physical mechanisms control amplification processes on monthly and decadal time scales, and models fail to capture such behavior; or (more plausibly) that residual errors in several observational data sets used here affect their representation of long-term trends.

Solar forcing of regional climate change during the Maunder Minimum.

We examine the climate response to solar irradiance changes between the late 17th-century Maunder Minimum and the late 18th century. Global average temperature changes are small (about 0.3 degrees to 0.4 degrees C) in both a climate model and empirical reconstructions. However, regional temperature changes are quite large. In the model, these occur primarily through a forced shift toward the low index state of the Arctic Oscillation/North Atlantic Oscillation as solar irradiance decreases. This leads to colder temperatures over the Northern Hemisphere continents, especially in winter (1 degrees to 2 degrees C), in agreement with historical records and proxy data for surface temperatures.

Sodium bicarbonate for the treatment of lactic acidosis.

Lactic acidosis often challenges the intensivist and is associated with a strikingly high mortality. Treatment involves discerning and correcting its underlying cause, ensuring adequate oxygen delivery to tissues, reducing oxygen demand through sedation and mechanical ventilation, and (most controversially) attempting to alkalinize the blood with IV sodium bicarbonate. Here we review the literature to answer the following questions: Is a low pH bad? Can sodium bicarbonate raise the pH in vivo? Does increasing the blood pH with sodium bicarbonate have any salutary effects? Does sodium bicarbonate have negative side effects? We find that the oft-cited rationale for bicarbonate use, that it might ameliorate the hemodynamic depression of metabolic acidemia, has been disproved convincingly. Further, given the lack of evidence supporting its use, we cannot condone bicarbonate administration for patients with lactic acidosis, regardless of the degree of acidemia.

Clinical examination reliably detects intrinsic positive end-expiratory pressure in critically ill, mechanically ventilated patients.

Critically ill patients requiring mechanical ventilation often develop intrinsic positive end-expiratory pressure (PEEPi). Methods for its detection include an expiratory flow waveform display (not always available), an esophageal pressure transducer (invasive), or a relaxed or paralyzed patient. We sought to determine the accuracy of clinical examination for detecting PEEPi. Examiners blinded to waveform analysis assessed patients for the presence of PEEPi by inspection/palpation and auscultation. If either inspection/palpation or auscultation demonstrated PEEPi, it was said to be present by clinical exam. Clinicians with various levels of experience (attending, resident, student) made 503 observations of 71 patients. Sensitivity (SENS), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios were determined for inspection/palpation, auscultation, and clinical exam. PEEPi was present during 69.8% of observations. SENS, SPEC, and PPV of clinical exam were 0.72, 0.91, and 0.95 respectively for the examiners as a whole. Likelihood ratio for PEEPi detection by clinical exam was 8.35. Attending intensivists displayed SPEC and PPV of 1.0. NPV was only 0.58 (likelihood ratio 0.31). We conclude that the clinical exam is very good for detecting PEEPi at all experience levels; and further, that the clinical exam is only modestly useful for ruling out PEEPi, therefore, other tests should be used if PEEPi is not detected by clinical exam.

Liberation from mechanical ventilation: a decade of progress.

Multiple complications associated with mechanical ventilation mandate that clinicians expeditiously define and reverse the pathophysiologic processes that precipitate respiratory failure and then, detect the earliest point that a patient can breathe without the ventilator. Over the past decade, numerous laboratory and clinical studies have been reported that may inform transformation of the "art of weaning" to the science of liberation. We review these studies and use them to formulate a systematic approach to assure early, safe, and successful liberation of patients from mechanical ventilation.

Inhaled helium-oxygen revisited: effect of inhaled helium-oxygen during the treatment of status asthmaticus in children.

OBJECTIVES: To assess the effects of breathing a low-density gas mixture on dyspnea and the pulsus paradoxus in children with status asthmaticus. DESIGN: In an urban academic tertiary referral center, 18 patients, aged 16 months to 16 years, who were being treated for status asthmaticus with continuously inhaled beta-agonist and intravenously administered methylprednisolone and had a pulsus paradoxus of greater than 15 mm Hg received either an 80%:20% helium-oxygen gas mixture (HELIOX patients) or room air (control patients) at 10 L/min by nonrebreathing face mask in a double-blind, randomized, controlled trial. In all patients, baseline data, including pulsus paradoxus (determined by sphygmomanometer or arterial catheter blood pressure readings), respiratory rate, heart rate, investigator-scored dyspnea index, and oxygen saturation, were compared with values obtained 15 minutes during and after intervention. In a subset of patients, peak flows before and after breathing HELIOX or room air were measured. When clinically indicated, arterial blood gases were obtained. RESULTS: The pulsus paradoxus (in millimeters of mercury) fell significantly from an initial mean value of 23.3 +/- 6.8 to 10.6 +/- 2.8 with HELIOX breathing (p < 0.001) and increased again to 18.5 +/- 7.3 after cessation of HELIOX. Peak flow increased 69.4% +/- 12.8% during HELIOX breathing (p < 0.05). The dyspnea index decreased from an initial mean value of 5.7 +/- 1.3 to 1.9 +/- 1.7 with HELIOX breathing (p < 0.0002) and increased again to 4.0 +/- 0.5 after cessation of HELIOX breathing. In control patients, there was no significant difference in pulsus paradoxus or dyspnea index at any time during the study period. Mechanical ventilation was averted in three patients in whom dyspnea lessened dramatically during breathing of HELIOX. CONCLUSION: During acute status asthmaticus, inhaled HELIOX significantly lowered the pulsus paradoxus, increased peak flow, and lessened the dyspnea index. Moreover, HELIOX spared three patients a planned intubation and caused no apparent side effects. Thus HELIOX reduces the work of breathing and may forestall respiratory failure in children with status asthmaticus, thus preventing the need for mechanical ventilation.

Pulmonary artery diastolic-occlusion pressure gradient is increased in acute pulmonary embolism.

OBJECTIVE: To assess the pulmonary artery (PA) diastolic-occlusion (wedge) pressure gradient in patients with acute pulmonary embolism and to evaluate this variable's diagnostic utility. DESIGN: Retrospective, clinical review. SETTING: Intensive care and cardiac catheterization units of a university medical center. INTERVENTIONS: None. PATIENTS: A series of 19 acute pulmonary embolism patients with concurrent right heart catheterization. Control groups consisted of 19 age-, sex-, and heart rate-matched critically ill controls who also underwent right heart catheterization, eight patients suspected of having pulmonary embolism who had negative pulmonary angiography and concurrent right heart catheterization, and 255 patients with a primary diagnosis of coronary artery disease who underwent right heart catheterization at the time of left heart catheterization. MEASUREMENTS AND MAIN RESULTS: Initial hemodynamics (systolic, diastolic, and mean systemic and pulmonary arterial pressures, occlusion pressure, PA diastolic-occlusion pressure gradient, cardiac output, systemic and pulmonary vascular resistances) were compared between cohorts. Other than differences in the PA diastolic-occlusion pressure gradients, no significant differences were identified between cohorts. Pulmonary embolism patients were found to have increased PA diastolic-occlusion pressure gradients (10 +/- 5 vs. 3 +/- 2 mm Hg for the critically ill controls [p < .0002], and 4 +/- 4 mm Hg for the coronary artery disease cohort [p < .0005]). However, no significant difference in PA diastolic-occlusion pressure gradient values was identified when patients with proven pulmonary embolism were compared with patients in whom pulmonary embolism was clinically suspected yet not confirmed by angiograms (10 +/- 9 mm Hg; NS). For three of 19 pulmonary embolism patients, no occlusion pressure could be obtained due to an inability to wedge the balloon tip; 13 of 16 patients had PA diastolic-occlusion pressure gradients of > or = 8 mm Hg. In the pulmonary embolism cohort, PA diastolic-occlusion pressure gradient correlated well with pulmonary vascular resistance (r2 = .50; p < .05), but not with cardiac output or heart rate. CONCLUSION: In the large number of patients with right heart catheters in whom the question of pulmonary embolism is raised, an increased PA diastolic-occlusion pressure gradient (especially > or = 8 mm Hg) may provide a clue to the diagnosis of pulmonary embolism, but is not specific for this diagnosis.

Heliox improves pulsus paradoxus and peak expiratory flow in nonintubated patients with severe asthma.

Heliox is a blend of helium and oxygen with a gas density less than that of air that decreases airway resistance (Raw) in patients ventilated for status asthmaticus. We tested whether breathing an 80:20 mixture of helium:oxygen would reduce pulsus paradoxus (PP) and increase peak expiratory flow (PEF) in patients presenting to the emergency room with an exacerbation of asthma. After receiving 30 min of beta-agonist aerosols and intravenously administered methylprednisolone, 27 patients whose PP remained greater than 15 mm Hg and whose PEF remained less than 250 L/min consented to breathe heliox or room air for 15 min. PP decreased and PEF increased with time in control patients, indicating a time-related effect of routine bronchodilator therapy (p < 0.05). PP decreased in 15 of 16 patients during heliox, and the change with heliox was significantly greater than that during air breathing (p < 0.01). PEF measured with a Wright's peak flow meter calibrated for heliox increased in all patients breathing heliox. Again, the increase in PEF during heliox breathing was significantly greater than the corresponding change in control patients breathing air (p < 0.001). To the extent that PP reflects the inspiratory fall in pleural pressure, this reduction in PP indicates a substantial reduction in inspiratory Raw when the less dense gas is inspired through narrowed bronchi having turbulent flow regimes. The 35% increase in PEF while breathing heliox signals a similar reduction in expiratory Raw, which might diminish the hyperinflation often observed during an exacerbation of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cooling on oxygen consumption in febrile critically ill patients.

Hyperthermic critically ill patients are commonly cooled to reduce their oxygen consumption (VO2). However, no previous studies in febrile humans have measured VO2 during cooling. We cooled 12 febrile, critically ill, mechanically ventilated patients while measuring VO2 and CO2 production (VCO2) by analysis of inspired and expired gases. All patients were mechanically ventilated for hypoxemic, hypercapneic, or shock-related respiratory failure and had a mean APACHE II score of 22.4 +/- 7.7. As temperature was reduced from 39.4 +/- 0.8 to 37.0 +/- 0.5 degrees C, VO2 decreased from 359.0 +/- 65.0 to 295.1 +/- 57.3 ml/min (p < 0.01) and VCO2 decreased from 303.6 +/- 43.6 to 243.5 +/- 37.3 ml/min (p < 0.01). The respiratory quotient (RQ) did not change significantly, and calculated energy expenditure decreased from 2,481 +/- 426 to 1,990 +/- 33 kcal/day (p < 0.01). In 7 patients with right heart catheters, cardiac output decreased from 8.4 +/- 3.2 to 6.5 +/- 1.8 L/min (p < 0.01) as the oxygen extraction fraction also tended to decrease from a mean of 28.2 +/- 6.8 to 23.4 +/- 4.7% (p = 0.12) during cooling. Accordingly, cooling the febrile patient unloads the cardiorespiratory system and, in situations of limited oxygen delivery or hypoxemic respiratory failure, may thus facilitate resuscitation and minimize the potential for hypoxic tissue injury.

The effect of mechanical ventilation on oxygen consumption in critically ill patients.

We measured oxygen consumption (VO2) during spontaneous breathing with continuous positive airway pressure (CPAP), assist control ventilation (AC), and control ventilation during muscle relaxation (AC-MR) in eight patients undergoing resuscitation from cardiopulmonary failure. VO2 decreased in all eight patients between CPAP and AC-MR; mean VO2 (255 +/- 92 ml/min) on CPAP exceeded that on AC-MR (209 +/- 79 ml/min) (p < 0.005). Compared with CPAP, AC without MR reduced VO2 in five of eight patients and mean VO2 (227 +/- 59 ml/min) tended to decrease (p = 0.14); clinical examination did not distinguish patients requiring MR to reduce VO2 further. If VO2 on CPAP approximates VO2 during spontaneous breathing, the difference between CPAP and AC-MR (VO2resp) represents the decrement of VO2 that can be obtained during muscle rest. Both VO2resp and the mechanical work performed by the ventilator on the respiratory system were increased to about five times the efficiencies reported for normal patients, but VO2resp did not correlate with the mechanical work because of a wide range of respiratory muscle efficiencies. These efficiencies are less than those reported in normal patients, which may reflect the effect of sepsis, acidemia, hypoxia, or other conditions in these patients. We conclude that mechanical ventilation with muscle relaxation reduces VO2 by more than 20%; beyond stabilizing pulmonary gas exchange, these interventions preserve limited O2 delivery (QO2) for other vital organs.

Treatment of bronchospasm by metered-dose inhaler albuterol in mechanically ventilated patients.

beta 2-agonist bronchodilators delivered by metered-dose inhalers (MDI) are commonly used in the treatment of bronchospasm in both intubated and nonintubated patients. Substantial data support the effectiveness of MDI delivery systems in nonintubated patients. However, few studies have examined the effectiveness of MDIs in intubated, mechanically ventilated patients. MDIs are often used in conjunction with a spacing device that may enhance delivery of drug to the airways, but few in vivo data have demonstrated efficacy of this delivery method in ventilated patients. We studied ten critically ill patients who had a peak (Ppeak) to pause (Ppause) gradient of more than 15 cm H2O during sedated, quiet breathing on assist control ventilation. We administered 5, 10, and 15 puffs (90 micrograms per puff) of MDI albuterol through a specific spacer (Aerovent) at 30-min intervals, while measuring resistive pressure (defined as Ppeak-Ppause) before and after treatments. Resistive airway pressure after 5 puffs decreased in nine of ten patients, from 25.1 +/- 7.2 to 20.8 +/- 5.6 cm H2O (p < 0.12). The addition of 10 more puffs further reduced resistive pressure in nine of nine patients from 20.8 +/- 5.6 to 19.0 +/- 4.4 (p < 0.01). Fifteen more puffs (30 cumulative puffs) did not result in further improvement (p > 0.5). A toxic reaction occurred in one patient (systolic blood pressure decreased 20 mm Hg) after 5 puffs of albuterol. We conclude that MDI administered through this specific spacer is effective in mechanically ventilated patients in doses up to 15 puffs, and that therapy should be titrated to effectiveness and toxicity.

Resistive pressure of a condenser humidifier in mechanically ventilated patients.

OBJECTIVES: Heat and moisture exchangers (or "nose" humidifiers) are commonly used to aid in the humidification of inspired gases of mechanically ventilated patients. These devices add resistance to the ventilator circuit that has heretofore not been quantified in critically ill patients. Accordingly, we determined the resistive pressures associated with new and old (but < 24 hrs in the circuit) humidifiers in 23 critically ill, mechanically ventilated patients. DESIGN: Prospective study. SETTING: Adult medical and surgical intensive care units at a university center. PATIENTS: Twenty-three critically ill, mechanically ventilated patients using a condenser humidifier between the wye and the endotracheal tube. INTERVENTIONS: Peak and plateau airway pressures were determined with the humidifier in place. These measurements were repeated without the humidifier, then after insertion of a fresh humidifier into the circuit. In five patients, measurements were repeated after humidifiers had remained in place for a full 24 hrs. MEASUREMENTS AND MAIN RESULTS: The new humidifiers increased the resistive pressure of the ventilator circuit by 4.8 +/- 2.6 cm H2O compared with no humidifier (p < .01) and had a mean resistance of 4.2 +/- 1.5 cm H2O/L/sec. Old humidifiers increased resistive pressure by 6.3 +/- 3.6 cm H2O compared with no humidifier (p < .01) and had a mean resistance of 5.1 +/- 1.8 cm H2O/L/sec. The resistive pressure doubled from 3.4 +/- 1.2 to 7.0 +/- 1.8 cm H2O (p < .01) in five patients in whom the humidifiers were left in the ventilator circuit for a full 24 hrs. CONCLUSIONS: The humidifier adds a significant resistance to the ventilator circuit which may lead to incorrect assessment of respiratory system mechanics, to inappropriate therapy (e.g., bronchodilators), or to difficulty in weaning from mechanical ventilation.

Cardiovascular physiology teaching: computer simulations vs. animal demonstrations.

The roots of physiology lie in laboratory observation, and physiology courses continue to rely on laboratory observation to provide students with practical information to correlate with their developing base of conceptual knowledge. To this end, animal laboratories provide a functioning example of interactions among organ systems and a source of data for student analysis. However, there are continuing objections to using animals for teaching, and animal labs are costly in time and effort. As an alternative laboratory tool, computer software can simulate the operation of multiple organ systems: responses to interventions illustrate intrinsic organ behavior and integrated systems physiology. Advantages of software over animal studies include alteration of variables that are not easily changed in vivo, repeated interventions, and cost-effective hands-on student access. Nevertheless, simulations miss intangible aspects of experimental physiology, and results depend critically on the assumptions of the model. We used both computer and animal demonstrations in teaching cardiovascular physiology to first-year medical students. The students rated both highly, but the computer-based session received a higher rating. We believe that both forms of teaching have educational merit. At the introductory level, the computer appears to provide an effective alternative.