As discussed in other articles in this supplement, Intrathoracic Pressure Regulation (IPR) is a novel therapy that leverages our natural physiology to increase perfusion in hypotensive patients and shows promise for improving outcomes for multiple etiologies. In this summary, I’ll briefly review how IPR works, results with current delivery methods and then discuss the future applications of this exciting therapy.
How IPR Works
The heart and lungs work together to create negative intrathoracic pressure (a vacuum), which aids in filling the heart. When we inhale, the diaphragm moves downward and the intercostal muscles cause the rib cage to expand, making the thoracic cavity larger.
The enlargement of the chest makes the pressure within the chest more negative, drawing air in and pulling some blood back to the heart, filling it to create cardiac output on the next contraction. This negative pressure also helps to lower intracranial pressure (ICP), making it easier to get blood flow to the brain.
Maintenance of negative filling pressure is essential to maintaining cardiac output. Recall that:
Blood Pressure = Cardiac Output x Peripheral Vascular Resistance
The heart only pumps out the blood that it can pull back through the negative pressure on the right side of the heart; thus, cardiac output is maintained by negative filling pressure. Anything that decreases the negative filling pressure reduces blood return to the heart (preload), lowers cardiac output, and may result in hypotension and shock. Conversely, anything that enhances the negative filling pressure increases preload and cardiac output and lowers ICP, offering a potential treatment for cardiac arrest and shock.
IPR does just that. By enhancing negative intrathoracic pressure, IPR has been shown in multiple studies to increase preload, lower ICP and increase blood flow to the brain. The potential of this therapy is significant, and early results look promising.
Current IPR Delivery Mechanisms & Results
Currently, IPR is delivered through impedance threshold devices (ITDs), which improve circulation in patients in cardiac arrest or shock. Studies from EMS agencies in Toledo, Ohio, and San Antonio, Texas, have shown that, when used in hypotensive patients, the ITD is well tolerated and can also increase blood pressure by up to 30%, while still allowing for permissive hypotension in traumatically injured patients. Contrary to fluids, the device appears to enhance blood flow, not just pressure.1,2
Dozens of animal and clinical studies have been conducted on the ITD in CPR showing enhanced blood flow to the heart and brain.3
In addition, studies have shown that when ACD-CPR is performed in combination with an ITD, it further enhances negative intrathoracic pressure, resulting in near-normal blood flow circulation to the heart and brain.4—6 The combination of ACD-CPR with an ITD was compared to conventional standard CPR alone in the ResQTrial, a National Institutes of Health-funded, multi-center, randomized, controlled trial, the results of which were published in 2011 in The Lancet.7
Overall survival to one year with standard CPR was near the national average of 5.9%; but with the ACD-CPR/ITD combination, survival improved 49% to 8.8% in adult patients with non-traumatic arrest of cardiac etiology. This data supports the concept that enhancing negative intrathoracic pressure improves perfusion and survival.
The Foundation for Innovative Approaches to Treating Cardiac Arrest
Enhanced blood flow improves perfusion and provides a more effective way to circulate drugs and deliver therapeutic hypothermia. Thus, the ACD-CPR/ITD combination opens the door to new ways to improve outcomes, even in patients with prolonged downtimes or resuscitation efforts. Let’s take a look at a few of those approaches.
Sodium nitroprusside, aka “Snappy” CPR: Shultz and colleagues have studied the use of sodium nitroprusside (SNP) during enhanced CPR (eCPR) in a porcine model.6 SNP is a potent vasodilator that could be detrimental if given when circulation is poor, but when used with eCPR (ACD-CPR/ITD), this device/drug combination (SNPeCPR, or “Snappy CPR”) dramatically improves circulation and short-term outcomes.
Studies have shown that in porcine models with extended downtimes (15 minutes of untreated v fib), animals receiving SNPeCPR had significantly improved 24-hour survival, better neurologic function and less post-resuscitation left ventricular dysfunction compared to animals receiving standard CPR.8 (See Figure 1 below.)
Overall performance score category comparing SNPeCPR to standard CPR8
Figure 1 shows results from a pre-clinical study in a porcine model by Schultz et al comparing outcomes in animals receiving standard CPR vs. subjects receiving SNPeCPR or “Snappy CPR,” which includes ACD-CPR with an ITD (eCPR) and sodium nitroprusside (SNP), a vasodilator.
“Stutter” CPR: A newly identified concern in the treatment of cardiac arrest is that the sudden influx of blood from CPR, following minutes without flow, can lead to reperfusion injury. Reperfusion is a recognized issue following organ transplantation; as a result, blood is gradually reintroduced to the new organ, allowing it time to get acclimated to a state of better perfusion. Reperfusion may also be a problem in cardiac arrests, particularly those with longer downtimes.
To assess whether cardiac arrest victims would benefit from a more gradual reintroduction of blood flow, Yannopoulos and colleagues used SNPeCPR (ACD-CPR/ITD and SNP) with intentional 20-second pauses during the first few minutes of CPR in pigs. Results showed a significant decrease in reperfusion injury and a significant increase in functional neurologic recovery compared to standard CPR.9
This “stutter” CPR approach is in stark contrast to the long-held tenet that all interruptions in CPR are harmful. It may be that in specific cases, controlled pauses at strategic times could actually be immensely helpful.
Adenosine: Other fascinating research is being conducted to determine whether uncommon resuscitation drugs and anesthetic gases may provide cardio- and neuro-protection during and after cardiac arrest. One such animal study looked at the impact of adenosine, a drug known to improve coronary blood flow but typically only used in EMS for the treatment of arrhythmias. The study compared outcomes in four groups of animals receiving treatment following 15 minutes of v fib:
1. Standard CPR
2. SNPeCPR
3. SNPeCPR + adenosine
4. SNPeCPR + adenosine with controlled pauses (“stutter” CPR)
The results were striking, as you can see in Figure 2 (see below).10
24-hour cerebral performance category score
Note: ¶ § Mean statistically significant difference compared to standard CPR, SNPeCPR and SNPeCPR + adenosine respectively.
Figure 2 illustrates from a pre-clinical study in a porcine model by Yannopoulos et al comparing 4 CPR methods:10 1) standard CPR (S-CPR); 2) ACD-CPR + ITD + sodium nitroprusside (SNPeCPR): 3) SNPeCPR + adenosine; and 4) Controlled pauses (CP) with SNPeCPR (CP-SNPeCPR) + adenosine, to assess outcomes.
“Head-up” CPR: Patients in cardiac arrest sometimes need to be tipped head-up or feet-up to be transported down stairs or in elevators. Investigators studying the impact of body position on cerebral circulation during cardiac arrest hypothesized that when a patient is treated in a head-up position, blood will need to flow against gravity and cerebral perfusion will be compromised.
One of the most exciting findings is that the use of the ITD with automated CPR (LUCAS 2 from Physio-Control) actually enhances venous return, cardiac output and cerebral perfusion during “head-up” CPR. Debaty and colleagues compared coronary and cerebral perfusion pressures in animals receiving CPR with a LUCAS 2 chest compression device and ITD in three positions: 30 degrees head down, supine, and 30 degrees head up. They found cerebral perfusion pressure was nearly doubled when the upper body was elevated to 30 degrees compared to when the body was supine (0 degrees) during CPR.11 (See Figure 3 below.)
Table angle and devices tested in “head up” CPR
Figure 3 shows how “head up” CPR involves raising the body to a 30 degree angle and performing automated CPR and an ITD.
Use of the ITD appears to work synergistically with gravity to improve hemodynamics. During chest compression, use of an ITD with automated CPR appears to improve cardiac output in conjunction with the 30-degree elevation. Automated chest decompression, gravity and use of the ITD help to lower ICP, resulting in reduced resistance to forward blood flow and better blood flow to the heart and brain.11 (See Figure 4 below.) Although more research is required to better understand the synergies of the devices with gravity, initial results show “head up” CPR could become a simple BLS technique to improve neurologic outcomes from cardiac arrest.
Relationship between body position and CPP and CePP
Figure 4: In a study by Debaty et al, the 30 degree head up angle showed significant improvements in both coronary (CPP) and cerebral perfusion pressures (CePP).11
The bottom line: Early research is clearly challenging long-standing beliefs about the treatment of cardiac arrest. We’ll need to keep our “heads up” and stay tuned to upcoming clinical trials of these device, drug and gravity combinations.
Future Technologies & Applications
So what’s next for IPR? We know the efficacy of an ITD is dependent upon the quality of CPR or the way a patient breathes through it. In addition, its therapeutic effect is only present during inhalation or chest compressions. Studies of a device that actively delivers ongoing IPR therapy, even if the patient is not breathing or undergoing chest compressions, are ongoing and results again look compelling.
A device still in studies, an intrathoracic pressure regulator (CirQLATOR from Advanced Circulatory), combines a continuous vacuum source and a pressure regulator with a means to provide intermittent positive pressure ventilation, resulting in a device that creates a controlled, ongoing therapeutic vacuum in between ventilations. In a clinical study of this device in cardiac arrest patients in Toledo, Ohio, patients who received the CirQLATOR exhibited significantly higher end tidal carbon dioxide levels than patients with the ITD alone.12 This technology may also be applicable to hypotensive patients who are not spontaneously breathing.
Another area of development for IPR: head injuries. Studies have shown IPR not only enhances circulation, it lowers ICP and increases cerebral perfusion pressure.13 The ability to do this noninvasively has naturally attracted the attention of neurologists interested in using the therapy in patients with head injuries or other cerebral insult. Solutions available today to lower ICP are invasive and have associated risks. In the future, it’s possible IPR therapy could be applied not only in the critical care setting, but also at the point of injury with the ResQGARD or CirQLATOR. A study to assess the impact of IPR with the CirQLATOR device on patients in the ICU with brain injury is currently underway.
Summary
Scientific advances are bringing new revelations to the management of critical conditions such as cardiac arrest and shock. Harnessing the mechanics of IPR and understanding their effect is resulting in improvements in cardiac resuscitation and therapy for hypotension in both hemorrhage and non-trauma shock states. Perfusion is improving. Our understanding of the relationship of IPR and cerebral perfusion is also expanding. Therapies that can improve forward flow and perfusion of vital organs are being utilized by BLS personnel. Noninvasive bridging tools that capture the benefit of IPR hold further potential to improve hemodynamics.
In the years to come, these and other insights gained through careful research will allow medical providers the world over to find new opportunities to save thousands of lives that would otherwise have been lost.
More Resuscitation from JEMS.com.
References
1. Convertino VA, Parquette B, Zeihr J, et al. Use of respiratory impedance in prehospital care of hypotensive patients associated with hemorrhage and trauma: A case series. J Trauma Acute Care Surg. 2012;73(2 Suppl 1):S54—S59.
2. Wampler D, Convertino VA, Weeks S, et al. Use of an impedance threshold device in spontaneously breathing patients with hypotension secondary to trauma: an observational cohort feasibility study. J Trauma Acute Care Surg. 2014;77(3 Suppl 2):S140—S145.
3. Yannopoulos D, Abella B, Duval S, et al. The effect of CPR quality: A potential confounder of CPR clinical trials. Circulation. 2014. [in press.]
4. Lurie KG, Coffeen P, Shultz J, et al. Improving active compression-decompression cardiopulmonary resuscitation with an inspiratory impedance valve. Circulation. 1995;91(6):1629—1632.
5. Lurie KG, Lindner KH. Recent advances in cardiopulmonary resuscitation. J Cardiovasc Electrophysiology. 1997;8(5):584-600.
6. Lurie K, Zielinksi T, McKnite S, et al. Improving the efficiency of cardiopulmonary resuscitation with an inspiratory impedance threshold valve. Crit Care Med. 2000;28(11):N207—N209.
7. Aufderheide TP, Frascone RJ, Wayne MA, et al. Standard cardiopulmonary resuscitation versus active compression-decompression cardiopulmonary resuscitation with augmentation of negative intrathoracic pressure for out-of-hospital cardiac arrest: A randomized trial. Lancet. 2011;377(9762):301—311.
8. Schultz J, Segal N, Kolbeck J, et al. Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation. Resuscitation. 2011;82 Suppl 2:S35—40.
9. Segal N, Matsuura T, Caldwell E, et al. Ischemic postconditioning at the initiation of cardiopulmonary resuscitation facilitates functional cardiac and cerebral recovery after prolonged untreated ventricular fibrillation. Resuscitation. 2012;83(11):1397—1403.
10. Yannopoulos D, Segal N, McKnite S, et al. Controlled pauses at the initiation of sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation. Crit Care Med. 2012;40(5):1562—1569.
11. Debaty G, Shin SD, Metzger A, et al. Gravity-assisted head up cardiopulmonary resuscitation improves cerebral blood flow and perfusion pressures in a porcine model of cardiac arrest. Circulation. 2014. [in press.]
12. Segal N, Parquette B, Ziehr J, et al. Intrathoracic pressure regulation during cadiopulmonary resuscitation: A feasibility case-series. Resuscitation. 2013;84(4):450—453.
13. Metzger AK, Herman M, McKnite S, et al. Improved cerebral perfusion pressures and 24-hr neurological survival in a porcine model of cardiac arrest with active compression-decompression cardiopulmonary resuscitation and augmentation of negative intrathoracic pressure. Crit Care Med. 2012;40(6);1851—1856.